Method for analyzing small molecule components of a complex mixture, and associated apparatus and computer program product

ABSTRACT

A method, apparatus, and computer-readable storage medium for analyzing component separation/mass spectrometer data for a sample having known characteristic includes analyzing reference ion data for a relationship between ion mass, retention time, and intensity. The analyzed data is added to a repository, wherein each ion therein has an intensity maxima within a characteristic retention time range for a characteristic ion mass. If the reference ion is in the repository, the range is modified according to the characteristic retention time of the reference ion intensity maxima. Based on the known characteristic, an ion expected in the sample is selected from the repository, and sample data is compared to data for the ion selected from the repository to determine whether the ion is present in the sample. The range in the repository is then modified according to the characteristic retention time of the intensity maxima for the ion present in the sample.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of International Patent Appl. No.PCT/IB2018/059982, filed Dec. 13, 2018, which International Applicationwas published by the International Bureau in English on Jun. 20, 2019,and which claims priority to U.S. Provisional Appl. No. 62/599,403,filed Dec. 15, 2017, both of which are incorporated by reference hereinin their entirety.

BACKGROUND OF THE DISCLOSURE Field of the Disclosure

The present disclosure relates to the field of analyzing small moleculecomponents in a complex mixture and, more particularly, to a method andassociated apparatus and computer program product for analyzing smallmolecule components of a complex mixture, with such small moleculeanalysis including metabolomics, which is the study of small moleculesproduced by an organism's metabolic processes, or other analysis ofsmall molecules produced through metabolism.

Description of Related Art

Metabolomics is the study of the small molecules, or metabolites,contained in a cell, tissue or organ (including fluids) and involved inprimary and intermediary metabolism. The term “metabolome” refers to thecollection of metabolites present in an organism. The human metabolomeencompasses native small molecules (natively biosynthesizeable,non-polymeric compounds) that are participants in general metabolicreactions and that are required for the maintenance, growth and normalfunction of a cell. Thus, metabolomics is a direct observation of thestatus of cellular physiology, and may thus be predictive of disease ina given organism. Subtle biochemical changes (including the presence ofselected metabolites) are inherent in a given disease. Therefore, theaccurate mapping of these changes to known pathways may allowresearchers to build a biochemical hypothesis for a disease. Based onthis hypothesis, the enzymes and proteins critical to the disease can beuncovered such that disease targets may be identified for treatment withtargeted pharmaceutical compounds or other therapy.

Molecular biology techniques for uncovering the biochemical processesunderlying disease have been centered on the genome, which consists ofthe genes that make up DNA, which is transcribed into RNA and thentranslated to proteins, which then make up the small molecules of thehuman metabolome. While genomics (study of the DNA-level biochemistry),transcript profiling (study of the RNA-level biochemistry), andproteomics (study of the protein-level biochemistry) are useful foridentification of disease pathways, these methods are complicated by thefact that there exist over 25,000 genes, 100,000 to 200,000 RNAtranscripts and up to 1,000,000 proteins in human cells. However, it isestimated that there may be as few as 2,500 small molecules in the humanmetabolome.

Thus, metabolomic technology provides a significant leap beyondgenomics, transcript profiling, and/or proteomics. With metabolomics,metabolites and their role in metabolism may be readily identified. Inthis context, the identification of disease targets may be expeditedwith greater accuracy relative to other known methods. The collection ofmetabolomic data for use in identifying disease pathways is generallyknown in the art, as described generally, for example, in U.S. Pat. Nos.7,005,255 and 7,329,489 to Metabolon, Inc., each entitled Methods forDrug Discovery, Disease Treatment, and Diagnosis Using Metabolomics.Additional uses for metabolomics data are described therein and include,for example, determining response to a therapeutic agent (i.e., a drug)or other xenobiotics, monitoring drug response, determining drug safety,and drug discovery. However, the collection and sorting of metabolomicdata taken from a variety of samples (e.g., from a patient population)consumes large amounts of time and computational power. For example,according to some known metabolomic techniques, spectrometry data forcertain samples is collected and plotted in three (or more) dimensions(i.e., sample properties that can be represented along an axis withrespect to other sample properties) and stored in an individual filecorresponding to each sample. This data is then, by individual file,compared to data corresponding to a plurality of known metabolites inorder to identify known metabolites that may be disease targets. Thedata may also be used for identification of toxic agents and/or drugmetabolites. Furthermore, such data may also be used to monitor theeffects of xenobiotics and/or used to monitor/measure/identify thexenobiotics and associated metabolites produced by processing(metabolizing) the xenobiotics. However, such conventional “file-based”methods (referring to the individual data file generated for eachsample) require the use of large amounts of computing power and memorycapacity to handle the screening of large numbers of known metabolites.Furthermore, “file-based” data handling may not lend itself to thecompilation of sample population data across a number of samplesbecause, according to known metabolomic data handling techniques, eachsample is analyzed independently, without taking into account subtlechanges in metabolite composition that may be more readily detectableacross a sample population. Furthermore, existing “file-based” methodmay have other limitations including: limited security and auditability;and poor data set consistency across multiple file copies. In addition,individual files may not support multiple indices (i.e., day collected,sample ID, control vs. treated, drug dose, etc.) such that all filesmust be scanned when only a particular subset is desired. Such“file-based” methods may thus be of limited assistance in usingpreviously-collected data to facilitate the analysis of data for newsamples.

These limitations in current metabolomic data analysis techniques maylead to the discarding of potentially relevant and/or valuablemetabolomic data that may be used to identify and classify particularmetabolites as disease targets. Specifically, spectrometry datacorresponding to a number of samples (such as tissue samples fromindividual human subjects) generally results in a large data filecorresponding to each sample, wherein each data file must then besubjected to an individual screening process with respect to a libraryof known metabolites. However, conventional systems do not readily allowfor the consolidation of spectrometry data from a number of samples forthe subjective evaluation of the data generated by the spectrometryprocesses. Thus, while a single file corresponding to an individualsample may be inconclusive, such data may be more telling if viewedsubjectively in a succinct format with respect to other samples within asample population.

One particular example of a limitation in current metabolomic dataanalysis techniques involves the identification of a metabolite in eachof a plurality of sample. In some instances, the identification of themetabolite involves analyzing the data file of each sample to determinewhether an indication (i.e., an intensity peak for a particular sampleion mass or sample component mass, observed at a particular retentiontime or range or retention times) of that metabolite exists within therespective data files. However, as previously noted, it may be difficultin “file based” data handling methods to verify whether the determinedindication is consistent across samples. For example, it may bedifficult to determine whether the identified intensity peaks arealigned with respect to retention time across the samples. Further,there may be instances where the indication (e.g., the intensity peak)is not clearly defined within the data file of one or more samples. Inthose instances, the indication (e.g., the intensity peak) may actuallyreflect the presence of more than one sample component and, as such, anyanalysis of those intensity peaks as a whole may be significantlyinaccurate. As such, the various assumptions and estimates, which may bedifficult to analyze for individual samples when using a file-base datahandling method, may result in an inaccurate indication of factors suchas the identification and quantity of that metabolite (or a plurality ofmetabolites) present over/across the plurality of the sample. In thisregard, such inaccuracy introduced into a metabolomics analysis at suchan early stage may lead to larger inaccuracies in subsequent steps oranalyses.

This collection of metabolomics data, as well as other empirical datarepresenting a knowledge base of metabolites including, for example,individual metabolite characteristics, situational metabolitecharacteristics, and interactional metabolite characteristics, alsoprovides an opportunity for using this trove of data to predict and/oridentify metabolites likely to be present in a particular sample, and/orto facilitate validation of the data collected for a particular sample.

Therefore, there exists a need for an improved apparatus and method forsolving the technical issues outlined above that are associated withconventional metabolomic data analysis systems. More particularly, thereexists a need for an apparatus and method capable of analyzingspectrometry data over/across samples, with the option of, but not theneed for, generating a separate data file for each sample. There alsoexists a need for an apparatus and method capable of allowing a user tosubjectively evaluate spectrometry data across a plurality of samples toidentify selected metabolites, for allowing the user to verify orotherwise determine the confidence in the identification of the selectedmetabolites, for allowing the user to examine the data associated withthe identification of the selected metabolites, for example, forsorting, grouping, and/or aligning purposes, and for allowing the userto determine additional information related to the identified selectedmetabolites, for instance, for quality control and consistencyverification purposes. There also exists a need for an improvedapparatus and method capable of more accurately identifying samplecomponents over/across samples from the acquired spectrometry data. Inaddition, there exists a need for better implementation of existingmetabolomics data, as well as other available metabolomics information,in the metabolomics analysis of subsequent samples.

SUMMARY OF THE DISCLOSURE

The above and other needs are met by aspects of the present disclosurewhich, in one aspect, provides a method of analyzing data for a samplehaving a known characteristic, wherein the data for the sample isobtained from a component separation and mass spectrometer system. Sucha method comprises analyzing data obtained from the component separationand mass spectrometer system for a reference ion, to determine arelationship between reference ion mass, retention time, and intensity,including intensity as a function of retention time for the referenceion mass, wherein the reference ion has an intensity maxima at acharacteristic retention time for the reference ion mass; adding theanalyzed data for the reference ion to an ion data repository, whereineach of the ions in the ion data repository has an intensity maximawithin a range of characteristic retention times for a characteristicion mass; modifying, if the reference ion was previously included in theion data repository, the range of characteristic retention times of thereference ion in the ion data repository, according to thecharacteristic retention time of the intensity maxima for the referenceion; selecting, via a user interface, one or more ions from the ion datarepository expected to be included in the sample based on the knowncharacteristic of the sample; comparing, on a display associated withthe user interface, data obtained from the component separation and massspectrometer system for the sample to data for each of the one or moreions selected from the ion data repository to determine whether any ofthe one or more ions is present in the sample; and modifying, via theuser interface, the range of characteristic retention times of each ofthe one or more ions determined to be present in the sample, in the datarepository, according to the characteristic retention time of theintensity maxima for a respective one of the one or more ions determinedto be present in the sample.

Another aspect of the present disclosure provides an apparatus foranalyzing data for a sample having a known characteristic, with the datafor the sample being obtained from a component separation and massspectrometer system, wherein the apparatus comprises a processor and amemory storing executable instructions that, in response to execution bythe processor, cause the apparatus to at least perform the steps of themethod aspect of the present disclosure.

A further aspect of the present disclosure provides a computer programproduct for analyzing data for a sample having a known characteristic,with the data for the sample being obtained from a component separationand mass spectrometer system, wherein the computer program productcomprises at least one non-transitory computer readable storage mediumhaving computer-readable program code stored thereon, thecomputer-readable program code comprising program code that isexecutable to at least perform the steps of the method aspect of thepresent disclosure.

The present disclosure thus includes, without limitation, the followingembodiments:

Embodiment 1: A method of analyzing data for a sample having a knowncharacteristic, the data for the sample being obtained from a componentseparation and mass spectrometer system, said method comprisinganalyzing data obtained from the component separation and massspectrometer system for a reference ion, to determine a relationshipbetween reference ion mass, retention time, and intensity, includingintensity as a function of retention time for the reference ion mass,the reference ion having an intensity maxima at a characteristicretention time for the reference ion mass; adding the analyzed data forthe reference ion to an ion data repository, each of the ions in the iondata repository having an intensity maxima within a range ofcharacteristic retention times for a characteristic ion mass; modifying,if the reference ion was previously included in the ion data repository,the range of characteristic retention times of the reference ion in theion data repository, according to the characteristic retention time ofthe intensity maxima for the reference ion; selecting, via a userinterface, one or more ions from the ion data repository expected to beincluded in the sample based on the known characteristic of the sample;comparing, on a display associated with the user interface, dataobtained from the component separation and mass spectrometer system forthe sample to data for each of the one or more ions selected from theion data repository to determine whether any of the one or more ions ispresent in the sample; and modifying, via the user interface, the rangeof characteristic retention times of each of the one or more ionsdetermined to be present in the sample, in the data repository,according to the characteristic retention time of the intensity maximafor a respective one of the one or more ions determined to be present inthe sample.Embodiment 2: The method of any preceding embodiment, or any combinationof preceding embodiments, comprising including the reference ion in thesample.

Embodiment 3: The method of any preceding embodiment, or any combinationof preceding embodiments, comprising: analyzing data obtained from thecomponent separation and mass spectrometer system for the sample todetermine a relationship between sample ion mass, retention time, andintensity, including intensity as a function of retention time for aselected sample ion mass, the selected sample ion mass being selectedvia the user interface; selecting, via the user interface, an ionpresent in the data for the sample, the selected ion having an intensitymaxima at a characteristic retention time for the selected sample ionmass; comparing the data for the selected ion to the selected one ormore ions in the ion data repository expected to be included in thesample based on the known characteristic of the sample, in order todetermine an identity of the selected ion; and modifying the range ofcharacteristic retention times of the ion in the ion data repositorycorresponding to the selected ion, according to the characteristicretention time of the intensity maxima for the selected ion.

Embodiment 4: The method of any preceding embodiment, or any combinationof preceding embodiments, wherein selecting one or more ions from theion data repository expected to be included in the sample based on theknown characteristic of the sample comprises querying the ion datarepository via the user interface to select the one or more ionstherefrom based upon a retention time of an intensity maxima of aselected ion from the data for the sample in relation to the range ofcharacteristic retention times of the intensity maxima of the one ormore ions in the ion data repository.Embodiment 5: The method of any preceding embodiment, or any combinationof preceding embodiments, wherein the sample comprises a plurality ofsamples in a sample run, and wherein selecting one or more ions from theion data repository expected to be included in the sample based on theknown characteristic of the sample comprises selecting the one or moreions from the ion data repository in relation to ions determined to bepresent in a first one of the plurality of samples, the selected one ormore ions related to ions determined to be present in a first one of theplurality of samples being used for comparison to the data for aremainder of the samples in the sample run.Embodiment 6: The method of any preceding embodiment, or any combinationof preceding embodiments, wherein comparing, on a display associatedwith the user interface, data obtained from the component separation andmass spectrometer system for the sample to data for each of the one ormore ions selected from the ion data repository comprises comparing, onthe display, a two dimensional plot of intensity as a function ofretention time for the sample to a two dimensional plot of intensity asa function of retention time for each of the one or more ions selectedfrom the ion data repository so as to provide a visual indication ofintensity maxima therebetween for determining whether any of the one ormore ions is present in the sample.Embodiment 7: The method of any preceding embodiment, or any combinationof preceding embodiments, wherein modifying, if the reference ion waspreviously included in the ion data repository, the range ofcharacteristic retention times of the reference ion in the ion datarepository, according to the characteristic retention time of theintensity maxima for the reference ion comprises reducing the range ofcharacteristic retention times if the characteristic retention time ofthe intensity maxima for the reference ion is within the range ofcharacteristic retention times; and determining whether any datadeviation factors in the component separation and mass spectrometersystem require consideration if the characteristic retention time of theintensity maxima for the reference ion is outside the range ofcharacteristic retention times.Embodiment 8: The method of any preceding embodiment, or any combinationof preceding embodiments, wherein the relationship between reference ionmass, retention time, and intensity, includes intensity as a function ofthe reference ion mass for a selected retention time, wherein the addingstep comprises adding the analyzed data for the reference ion to an iondata repository such that each of the ions in the ion data repositoryhave the intensity maxima within a range of characteristic ion massesfor a characteristic retention time, and wherein the modifying stepcomprises modifying, if the reference ion was previously included in theion data repository, the range of characteristic ion masses of thereference ion in the ion data repository, according to thecharacteristic ion mass of the intensity maxima for the reference ion.Embodiment 9: The method of any preceding embodiment, or any combinationof preceding embodiments, wherein selecting one or more ions from theion data repository comprises comparing the known characteristic toempirical data included in the ion data repository, the empirical dataincluding relational information between known characteristics and ions,and determining therefrom the one or more ions corresponding to theknown characteristic of the sample.Embodiment 10: The method of any preceding embodiment, or anycombination of preceding embodiments, wherein, after comparing data forthe sample to data for the one or more ions from the ion data repositoryand determining whether any of the one or more ions is present in thesample, the method comprises adding empirical data associated with thesample to the ion data repository in relation to the any of the one ormore ions determined to be present in the sample.Embodiment 11: The method of any preceding embodiment, or anycombination of preceding embodiments, comprising analyzing data obtainedfrom the component separation and mass spectrometer system for an anchorsample, the anchor sample being defined as a consistent,previously-characterized sample, to determine a component ion of theanchor sample and a relationship between component ion mass, retentiontime, and intensity, including intensity as a function of retention timefor the component ion mass, the component ion having an intensity maximaat a characteristic component ion retention time for the component ionmass.Embodiment 12: The method of any preceding embodiment, or anycombination of preceding embodiments, wherein the component ion mass issubstantially equal to the characteristic ion mass of one of the one ormore ions determined to be in the sample, and the method comprisescomparing the intensity maxima for the component ion at thecharacteristic component ion retention time, to the intensity maxima forthe one of the one or more ions determined to be in the sample at thecharacteristic retention time, wherein if the intensity maxima for thecomponent ion and the one of the one or more ions determined to be inthe sample are substantially similar, then the one of the one or moreions determined to be in the sample is designated as an artifact ion inthe sample.Embodiment 13: The method of any preceding embodiment, or anycombination of preceding embodiments, wherein the anchor samplecomprises water.Embodiment 14: The method of any preceding embodiment, or anycombination of preceding embodiments, wherein the sample comprises aplurality of samples in a sample run, wherein the method comprisesanalyzing the plurality of samples in the sample run to determine apresence of one of the one or more ions from the ion data repositorydetermined to be present in a first one of the plurality of samples,across the plurality of samples, and wherein if a threshold quantity ofthe samples in the plurality of samples does not include the one of theone or more ions from the ion data repository determined to be presentin the first one of the plurality of samples, then the one of the one ormore ions determined to be present in the first one of the plurality ofsamples is designated as sparse ion in the plurality of samples.Embodiment 15: The method of any preceding embodiment, or anycombination of preceding embodiments, wherein the sample comprises aplurality of samples in a sample run, and wherein the method comprisesanalyzing data obtained from the component separation and massspectrometer system for each sample to determine a relationship betweensample ion mass, retention time, and intensity, including intensity as afunction of retention time for a selected sample ion mass, the selectedsample ion mass being selected via the user interface; analyzing theintensity as the function of retention time for the selected sample ionmass for each of the samples, across the plurality of samples, toidentify an intensity maxima within a predicted range of retention timesfor each sample, the predicted range of retention times including anexpected intensity maxima retention time therein for the selected sampleion mass; identifying, for each sample, an actual retention time of theintensity maxima in relation to the expected intensity maxima retentiontime; and determining whether the actual retention times of theintensity maxima of two or more consecutive samples of the plurality ofsamples in the sample run demonstrate an identifiable pattern withrespect to the expected intensity maxima retention time.Embodiment 16: The method of any preceding embodiment, or anycombination of preceding embodiments, wherein the identifiable patternof the actual retention times of the intensity maxima of the two or moreconsecutive samples, with respect to the expected intensity maximaretention time, comprises a shift wherein the actual retention times ofthe intensity maxima are substantially consistently offset from theexpected intensity maxima retention time, or a drift wherein the actualretention times of the intensity maxima are offset by a non-constantfunction from the expected intensity maxima retention time, and whereinthe method comprises correcting the offset of the actual retention timeof the intensity maxima of each of the plurality of samples in thesample run according to the identifiable pattern.Embodiment 17: The method of any preceding embodiment, or anycombination of preceding embodiments, wherein the identifiable patternof the actual retention times of the intensity maxima of the two or moreconsecutive samples, with respect to the expected intensity maximaretention time, comprises an offset from the expected intensity maximaretention time, the offset differing between two subsets of two or moreconsecutive samples in the sample run, and wherein the method comprisescorrecting the offset of the actual retention times of the intensitymaxima of each of the plurality of samples in the sample run accordingto the identifiable pattern of one of the two subsets having a majorityof the samples in the sample run.Embodiment 18: The method of any preceding embodiment, or anycombination of preceding embodiments, wherein, if comparing dataobtained from the component separation and mass spectrometer system forthe sample to data for each of the one or more ions selected from theion data repository to determine whether any of the one or more ions ispresent in the sample results in none of the one or more ions beingpresent in the sample, then the method comprises resolving an instrumenterror associated with the component separation and mass spectrometersystem and re-running the sample through the component separation andmass spectrometer system to obtain replacement data for the sample.Embodiment 19: The method of any preceding embodiment, or anycombination of preceding embodiments, comprising displaying, on thedisplay associated with the user interface, the corrected offset of theactual retention time of the intensity maxima of each of the pluralityof samples in the sample run according to the identifiable pattern toprovide a visualization of the corrected actual retention time of theintensity maxima of each of the plurality of samples across theplurality of samples in the sample run.Embodiment 20: An apparatus for analyzing data for a sample having aknown characteristic, the data for the sample being obtained from acomponent separation and mass spectrometer system, the apparatuscomprising a processor and a memory storing executable instructionsthat, in response to execution by the processor, cause the apparatus toat least perform the steps of analyzing data obtained from the componentseparation and mass spectrometer system for a reference ion, todetermine a relationship between reference ion mass, retention time, andintensity, including intensity as a function of retention time for thereference ion mass, the reference ion having an intensity maxima at acharacteristic retention time for the reference ion mass; adding theanalyzed data for the reference ion to an ion data repository, each ofthe ions in the ion data repository having an intensity maxima within arange of characteristic retention times for a characteristic ion mass;modifying, if the reference ion was previously included in the ion datarepository, the range of characteristic retention times of the referenceion in the ion data repository, according to the characteristicretention time of the intensity maxima for the reference ion; selecting,via a user interface associated with the apparatus, one or more ionsfrom the ion data repository expected to be included in the sample basedon the known characteristic of the sample; comparing, on a displayassociated with the user interface, data obtained from the componentseparation and mass spectrometer system for the sample to data for eachof the one or more ions selected from the ion data repository todetermine whether any of the one or more ions is present in the sample;and modifying, via the user interface, the range of characteristicretention times of each of the one or more ions determined to be presentin the sample, in the data repository, according to the characteristicretention time of the intensity maxima for a respective one of the oneor more ions determined to be present in the sample.Embodiment 21: The apparatus of any preceding embodiment, or anycombination of preceding embodiments, wherein the reference ion isincluded in the sample.Embodiment 22: The apparatus of any preceding embodiment, or anycombination of preceding embodiments, wherein the memory storesexecutable instructions that, in response to execution by the processor,cause the apparatus to further perform the steps of analyzing dataobtained from the component separation and mass spectrometer system forthe sample to determine a relationship between sample ion mass,retention time, and intensity, including intensity as a function ofretention time for a selected sample ion mass, the selected sample ionmass being selected via the user interface; selecting, via the userinterface, an ion present in the data for the sample, the selected ionhaving an intensity maxima at a characteristic retention time for theselected sample ion mass; comparing the data for the selected ion to theselected one or more ions in the ion data repository expected to beincluded in the sample based on the known characteristic of the sample,in order to determine an identity of the selected ion; and modifying therange of characteristic retention times of the ion in the ion datarepository corresponding to the selected ion, according to thecharacteristic retention time of the intensity maxima for the selectedion.Embodiment 23: The apparatus of any preceding embodiment, or anycombination of preceding embodiments, wherein the memory storesexecutable instructions that, in response to execution by the processor,cause the apparatus to further perform the step of querying the ion datarepository via the user interface to select the one or more ionstherefrom based upon a retention time of an intensity maxima of aselected ion from the data for the sample in relation to the range ofcharacteristic retention times of the intensity maxima of the one ormore ions in the ion data repository.Embodiment 24: The apparatus of any preceding embodiment, or anycombination of preceding embodiments, wherein the sample comprises aplurality of samples in a sample run, and wherein the memory storesexecutable instructions that, in response to execution by the processor,cause the apparatus to further perform the step of selecting the one ormore ions from the ion data repository in relation to ions determined tobe present in a first one of the plurality of samples, the selected oneor more ions related to ions determined to be present in a first one ofthe plurality of samples being used for comparison to the data for aremainder of the samples in the sample run.Embodiment 25: The apparatus of any preceding embodiment, or anycombination of preceding embodiments, wherein the memory storesexecutable instructions that, in response to execution by the processor,cause the apparatus to further perform the step of comparing, on thedisplay, a two dimensional plot of intensity as a function of retentiontime for the sample to a two dimensional plot of intensity as a functionof retention time for each of the one or more ions selected from the iondata repository so as to provide a visual indication of intensity maximatherebetween for determining whether any of the one or more ions ispresent in the sample.Embodiment 26: The apparatus of any preceding embodiment, or anycombination of preceding embodiments, wherein the memory storesexecutable instructions that, in response to execution by the processor,cause the apparatus to further perform the steps of reducing the rangeof characteristic retention times if the characteristic retention timeof the intensity maxima for the reference ion is within the range ofcharacteristic retention times; and determining whether any datadeviation factors in the component separation and mass spectrometersystem require consideration if the characteristic retention time of theintensity maxima for the reference ion is outside the range ofcharacteristic retention times.Embodiment 27: The apparatus of any preceding embodiment, or anycombination of preceding embodiments, wherein the relationship betweenreference ion mass, retention time, and intensity, includes intensity asa function of the reference ion mass for a selected retention time, andwherein the memory stores executable instructions that, in response toexecution by the processor, cause the apparatus to further perform thesteps of adding the analyzed data for the reference ion to an ion datarepository such that each of the ions in the ion data repository havethe intensity maxima within a range of characteristic ion masses for acharacteristic retention time; and modifying, if the reference ion waspreviously included in the ion data repository, the range ofcharacteristic ion masses of the reference ion in the ion datarepository, according to the characteristic ion mass of the intensitymaxima for the reference ion.Embodiment 28: The apparatus of any preceding embodiment, or anycombination of preceding embodiments, wherein the memory storesexecutable instructions that, in response to execution by the processor,cause the apparatus to further perform the steps of comparing the knowncharacteristic to empirical data included in the ion data repository,the empirical data including relational information between knowncharacteristics and ions; and determining therefrom the one or more ionscorresponding to the known characteristic of the sample.Embodiment 29: The apparatus of any preceding embodiment, or anycombination of preceding embodiments, wherein the memory storesexecutable instructions that, in response to execution by the processor,cause the apparatus to further perform the step of adding empirical dataassociated with the sample to the ion data repository in relation to theany of the one or more ions determined to be present in the sample,after comparing data for the sample to data for the one or more ionsfrom the ion data repository and determining whether any of the one ormore ions is present in the sample.Embodiment 30: The apparatus of any preceding embodiment, or anycombination of preceding embodiments, wherein the memory storesexecutable instructions that, in response to execution by the processor,cause the apparatus to further perform the step of analyzing dataobtained from the component separation and mass spectrometer system foran anchor sample, the anchor sample being defined as a consistent,previously-characterized sample, to determine a component ion of theanchor sample and a relationship between component ion mass, retentiontime, and intensity, including intensity as a function of retention timefor the component ion mass, the component ion having an intensity maximaat a characteristic component ion retention time for the component ionmass.Embodiment 31: The apparatus of any preceding embodiment, or anycombination of preceding embodiments, wherein the component ion mass issubstantially equal to the characteristic ion mass of one of the one ormore ions determined to be in the sample, and wherein the memory storesexecutable instructions that, in response to execution by the processor,cause the apparatus to further perform the step of comparing theintensity maxima for the component ion at the characteristic componention retention time, to the intensity maxima for the one of the one ormore ions determined to be in the sample at the characteristic retentiontime, wherein if the intensity maxima for the component ion and the oneof the one or more ions determined to be in the sample are substantiallysimilar, then the one of the one or more ions determined to be in thesample is designated as an artifact ion in the sample.Embodiment 32: The apparatus of any preceding embodiment, or anycombination of preceding embodiments, wherein the anchor samplecomprises water.Embodiment 33: The apparatus of any preceding embodiment, or anycombination of preceding embodiments, wherein the sample comprises aplurality of samples in a sample run, and wherein the memory storesexecutable instructions that, in response to execution by the processor,cause the apparatus to further perform the step of analyzing theplurality of samples in the sample run to determine a presence of one ofthe one or more ions from the ion data repository determined to bepresent in a first one of the plurality of samples, across the pluralityof samples, wherein if a threshold quantity of the samples in theplurality of samples does not include the one of the one or more ionsfrom the ion data repository determined to be present in the first oneof the plurality of samples, then the one of the one or more ionsdetermined to be present in the first one of the plurality of samples isdesignated as sparse ion in the plurality of samples.Embodiment 34: The apparatus of any preceding embodiment, or anycombination of preceding embodiments, wherein the sample comprises aplurality of samples in a sample run, and wherein the memory storesexecutable instructions that, in response to execution by the processor,cause the apparatus to further perform the steps of analyzing dataobtained from the component separation and mass spectrometer system foreach sample to determine a relationship between sample ion mass,retention time, and intensity, including intensity as a function ofretention time for a selected sample ion mass, the selected sample ionmass being selected via the user interface; analyzing the intensity asthe function of retention time for the selected sample ion mass for eachof the samples, across the plurality of samples, to identify anintensity maxima within a predicted range of retention times for eachsample, the predicted range of retention times including an expectedintensity maxima retention time therein for the selected sample ionmass; identifying, for each sample, an actual retention time of theintensity maxima in relation to the expected intensity maxima retentiontime; and determining whether the actual retention times of theintensity maxima of two or more consecutive samples of the plurality ofsamples in the sample run demonstrate an identifiable pattern withrespect to the expected intensity maxima retention time.Embodiment 35: The apparatus of any preceding embodiment, or anycombination of preceding embodiments, wherein the identifiable patternof the actual retention times of the intensity maxima of the two or moreconsecutive samples, with respect to the expected intensity maximaretention time, comprises a shift wherein the actual retention times ofthe intensity maxima are substantially consistently offset from theexpected intensity maxima retention time, or a drift wherein the actualretention times of the intensity maxima are offset by a non-constantfunction from the expected intensity maxima retention time, and whereinthe memory stores executable instructions that, in response to executionby the processor, cause the apparatus to further perform the step ofcorrecting the offset of the actual retention time of the intensitymaxima of each of the plurality of samples in the sample run accordingto the identifiable pattern.Embodiment 36: The apparatus of any preceding embodiment, or anycombination of preceding embodiments, wherein the identifiable patternof the actual retention times of the intensity maxima of the two or moreconsecutive samples, with respect to the expected intensity maximaretention time, comprises an offset from the expected intensity maximaretention time, the offset differing between two subsets of two or moreconsecutive samples in the sample run, and wherein the memory storesexecutable instructions that, in response to execution by the processor,cause the apparatus to further perform the step of correcting the offsetof the actual retention times of the intensity maxima of each of theplurality of samples in the sample run according to the identifiablepattern of one of the two subsets having a majority of the samples inthe sample run.Embodiment 37: The apparatus of any preceding embodiment, or anycombination of preceding embodiments, wherein, if comparing dataobtained from the component separation and mass spectrometer system forthe sample to data for each of the one or more ions selected from theion data repository to determine whether any of the one or more ions ispresent in the sample results in none of the one or more ions beingpresent in the sample, the memory stores executable instructions that,in response to execution by the processor, then cause the apparatus tofurther perform the step of resolving an instrument error associatedwith the component separation and mass spectrometer system andre-running the sample through the component separation and massspectrometer system to obtain replacement data for the sample.Embodiment 38: The apparatus of any preceding embodiment, or anycombination of preceding embodiments, wherein the memory storesexecutable instructions that, in response to execution by the processor,cause the apparatus to further perform the step of displaying, on thedisplay associated with the user interface, the corrected offset of theactual retention time of the intensity maxima of each of the pluralityof samples in the sample run according to the identifiable pattern toprovide a visualization of the corrected actual retention time of theintensity maxima of each of the plurality of samples across theplurality of samples in the sample run.Embodiment 39: A computer program product for analyzing data for asample having a known characteristic, the data for the sample beingobtained from a component separation and mass spectrometer system, thecomputer program product comprising at least one non-transitory computerreadable storage medium having computer-readable program code storedthereon, the computer-readable program code comprising program code forperforming the steps of analyzing data obtained from the componentseparation and mass spectrometer system for a reference ion, todetermine a relationship between reference ion mass, retention time, andintensity, including intensity as a function of retention time for thereference ion mass, the reference ion having an intensity maxima at acharacteristic retention time for the reference ion mass; adding theanalyzed data for the reference ion to an ion data repository, each ofthe ions in the ion data repository having an intensity maxima within arange of characteristic retention times for a characteristic ion mass;modifying, if the reference ion was previously included in the ion datarepository, the range of characteristic retention times of the referenceion in the ion data repository, according to the characteristicretention time of the intensity maxima for the reference ion; selecting,via a user interface associated with the apparatus, one or more ionsfrom the ion data repository expected to be included in the sample basedon the known characteristic of the sample; comparing, on a displayassociated with the user interface, data obtained from the componentseparation and mass spectrometer system for the sample to data for eachof the one or more ions selected from the ion data repository todetermine whether any of the one or more ions is present in the sample;and modifying, via the user interface, the range of characteristicretention times of each of the one or more ions determined to be presentin the sample, in the data repository, according to the characteristicretention time of the intensity maxima for a respective one of the oneor more ions determined to be present in the sample.Embodiment 40: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein the reference ionis included in the sample.Embodiment 41: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein the computerprogram product comprises program code for analyzing data obtained fromthe component separation and mass spectrometer system for the sample todetermine a relationship between sample ion mass, retention time, andintensity, including intensity as a function of retention time for aselected sample ion mass, the selected sample ion mass being selectedvia the user interface; selecting, via the user interface, an ionpresent in the data for the sample, the selected ion having an intensitymaxima at a characteristic retention time for the selected sample ionmass; comparing the data for the selected ion to the selected one ormore ions in the ion data repository expected to be included in thesample based on the known characteristic of the sample, in order todetermine an identity of the selected ion; and modifying the range ofcharacteristic retention times of the ion in the ion data repositorycorresponding to the selected ion, according to the characteristicretention time of the intensity maxima for the selected ion.Embodiment 42: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein the computerprogram product comprises program code for querying the ion datarepository via the user interface to select the one or more ionstherefrom based upon a retention time of an intensity maxima of aselected ion from the data for the sample in relation to the range ofcharacteristic retention times of the intensity maxima of the one ormore ions in the ion data repository.Embodiment 43: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein the samplecomprises a plurality of samples in a sample run, and wherein thecomputer program product comprises program code for selecting the one ormore ions from the ion data repository in relation to ions determined tobe present in a first one of the plurality of samples, the selected oneor more ions related to ions determined to be present in a first one ofthe plurality of samples being used for comparison to the data for aremainder of the samples in the sample run.Embodiment 44: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein the computerprogram product comprises program code for comparing a two dimensionalplot of intensity as a function of retention time for the sample to atwo dimensional plot of intensity as a function of retention time foreach of the one or more ions selected from the ion data repository so asto provide a visual indication of intensity maxima therebetween fordetermining whether any of the one or more ions is present in thesample.Embodiment 45: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein the computerprogram product comprises program code for comparing, on the display, atwo dimensional plot of intensity as a function of retention time forthe sample to a two dimensional plot of intensity as a function ofretention time for each of the one or more ions selected from the iondata repository so as to provide a visual indication of intensity maximatherebetween for determining whether any of the one or more ions ispresent in the sample.Embodiment 46: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein the computerprogram product comprises program code for modifying, if the referenceion was previously included in the ion data repository, the range ofcharacteristic retention times of the reference ion in the ion datarepository, according to the characteristic retention time of theintensity maxima for the reference ion comprises reducing the range ofcharacteristic retention times if the characteristic retention time ofthe intensity maxima for the reference ion is within the range ofcharacteristic retention times; and determining whether any datadeviation factors in the component separation and mass spectrometersystem require consideration if the characteristic retention time of theintensity maxima for the reference ion is outside the range ofcharacteristic retention times.Embodiment 47: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein the relationshipbetween reference ion mass, retention time, and intensity, includesintensity as a function of the reference ion mass for a selectedretention time, and wherein the computer program product comprisesprogram code for adding the analyzed data for the reference ion to anion data repository such that each of the ions in the ion datarepository have the intensity maxima within a range of characteristicion masses for a characteristic retention time; and modifying, if thereference ion was previously included in the ion data repository, therange of characteristic ion masses of the reference ion in the ion datarepository, according to the characteristic ion mass of the intensitymaxima for the reference ion.Embodiment 48: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein the computerprogram product comprises program code for comparing the knowncharacteristic to empirical data included in the ion data repository,the empirical data including relational information between knowncharacteristics and ions; and determining therefrom the one or more ionscorresponding to the known characteristic of the sample.Embodiment 49: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein, after comparingdata for the sample to data for the one or more ions from the ion datarepository and determining whether any of the one or more ions ispresent in the sample, the computer program product comprises programcode for adding empirical data associated with the sample to the iondata repository in relation to the any of the one or more ionsdetermined to be present in the sample.Embodiment 50: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein the computerprogram product comprises program code for analyzing data obtained fromthe component separation and mass spectrometer system for an anchorsample, the anchor sample being defined as a consistent,previously-characterized sample, to determine a component ion of theanchor sample and a relationship between component ion mass, retentiontime, and intensity, including intensity as a function of retention timefor the component ion mass, the component ion having an intensity maximaat a characteristic component ion retention time for the component ionmass.Embodiment 51: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein the component ionmass is substantially equal to the characteristic ion mass of one of theone or more ions determined to be in the sample, and wherein thecomputer program product comprises program code for comparing theintensity maxima for the component ion at the characteristic componention retention time, to the intensity maxima for the one of the one ormore ions determined to be in the sample at the characteristic retentiontime, wherein if the intensity maxima for the component ion and the oneof the one or more ions determined to be in the sample are substantiallysimilar, then the one of the one or more ions determined to be in thesample is designated as an artifact ion in the sample.Embodiment 52: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein the anchor samplecomprises water.Embodiment 53: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein the samplecomprises a plurality of samples in a sample run, and wherein thecomputer program product comprises program code for analyzing theplurality of samples in the sample run to determine a presence of one ofthe one or more ions from the ion data repository determined to bepresent in a first one of the plurality of samples, across the pluralityof samples, wherein if a threshold quantity of the samples in theplurality of samples does not include the one of the one or more ionsfrom the ion data repository determined to be present in the first oneof the plurality of samples, then the one of the one or more ionsdetermined to be present in the first one of the plurality of samples isdesignated as sparse ion in the plurality of samples.Embodiment 54: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein the samplecomprises a plurality of samples in a sample run, and wherein thecomputer program product comprises program code for analyzing dataobtained from the component separation and mass spectrometer system foreach sample to determine a relationship between sample ion mass,retention time, and intensity, including intensity as a function ofretention time for a selected sample ion mass, the selected sample ionmass being selected via the user interface; analyzing the intensity asthe function of retention time for the selected sample ion mass for eachof the samples, across the plurality of samples, to identify anintensity maxima within a predicted range of retention times for eachsample, the predicted range of retention times including an expectedintensity maxima retention time therein for the selected sample ionmass; identifying, for each sample, an actual retention time of theintensity maxima in relation to the expected intensity maxima retentiontime; and determining whether the actual retention times of theintensity maxima of two or more consecutive samples of the plurality ofsamples in the sample run demonstrate an identifiable pattern withrespect to the expected intensity maxima retention time.Embodiment 55: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein the identifiablepattern of the actual retention times of the intensity maxima of the twoor more consecutive samples, with respect to the expected intensitymaxima retention time, comprises a shift wherein the actual retentiontimes of the intensity maxima are substantially consistently offset fromthe expected intensity maxima retention time, or a drift wherein theactual retention times of the intensity maxima are offset by anon-constant function from the expected intensity maxima retention time,and wherein the computer program product comprises program code forcorrecting the offset of the actual retention time of the intensitymaxima of each of the plurality of samples in the sample run accordingto the identifiable pattern.Embodiment 56: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein the identifiablepattern of the actual retention times of the intensity maxima of the twoor more consecutive samples, with respect to the expected intensitymaxima retention time, comprises an offset from the expected intensitymaxima retention time, the offset differing between two subsets of twoor more consecutive samples in the sample run, and wherein the computerprogram product comprises program code for correcting the offset of theactual retention times of the intensity maxima of each of the pluralityof samples in the sample run according to the identifiable pattern ofone of the two subsets having a majority of the samples in the samplerun.Embodiment 57: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein, if comparing dataobtained from the component separation and mass spectrometer system forthe sample to data for each of the one or more ions selected from theion data repository to determine whether any of the one or more ions ispresent in the sample results in none of the one or more ions beingpresent in the sample, the computer program product comprises programcode for then resolving an instrument error associated with thecomponent separation and mass spectrometer system and re-running thesample through the component separation and mass spectrometer system toobtain replacement data for the sample.Embodiment 58: The computer program product of any preceding embodiment,or any combination of preceding embodiments, wherein the computerprogram product comprises program code for displaying, on the displayassociated with the user interface, the corrected offset of the actualretention time of the intensity maxima of each of the plurality ofsamples in the sample run according to the identifiable pattern toprovide a visualization of the corrected actual retention time of theintensity maxima of each of the plurality of samples across theplurality of samples in the sample run.

These and other features, aspects, and advantages of the presentdisclosure will be apparent from a reading of the following detaileddescription together with the accompanying drawings, which are brieflydescribed below. The present disclosure includes any combination of two,three, four, or more features or elements set forth in this disclosureor recited in any one or more of the claims, regardless of whether suchfeatures or elements are expressly combined or otherwise recited in aspecific embodiment description or claim herein. This disclosure isintended to be read holistically such that any separable features orelements of the disclosure, in any of its aspects and embodiments,should be viewed as intended to be combinable, unless the context of thedisclosure clearly dictates otherwise.

Thus, the apparatuses, methods, and computer program products foranalyzing data for a sample having a known characteristic, with the databeing obtained from a component separation and mass spectrometer systemand according to aspects of the present disclosure provide these andother advantages, as detailed further herein. Importantly, theseadvantages include the ability to dynamically and autonomously identifyand verify ions, compounds or other components present in a samplehaving a known characteristic, with increased quality and consistency ofanalysis results. These advantages also include the capability ofincreasing curation/verification speed for identified ions, compounds orcomponents of the sample, while lowering the manual manipulation of datarequired for verification/curation, for example, by providing a visualverification process.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

Having thus described the disclosure in general terms, reference willnow be made to the accompanying drawings, which are not necessarilydrawn to scale, and wherein:

FIG. 1 schematically illustrates a system according to one aspect of thepresent disclosure including a memory device having a database, aprocessor device, and a user interface (display), in communication witha spectrometry device;

FIG. 2 schematically illustrates a three-dimensional plot ofspectrometry data associated with one exemplary sample;

FIG. 3 schematically illustrates a two-dimensional profile plot for oneexemplary sample that may be determined from the correspondingthree-dimensional plot of spectrometry data for that sample according tosome aspects of the present disclosure;

FIG. 4 schematically illustrates a two-dimensional profile plot for oneexemplary sample that may be determined from the correspondingthree-dimensional plot of spectrometry data for that sample according tosome aspects of the present disclosure;

FIG. 5 schematically illustrates an operational flow of the apparatuses,methods, and computer program products of one exemplary aspect of thepresent disclosure;

FIG. 6 schematically illustrates a two dimensional plot of intensity asa function of retention time for the data associated with the sample toa two dimensional plot of intensity as a function of retention time forthe data associated with each of the one or more ions selected from theion data repository, according to one aspect of the present disclosure;

FIG. 7 schematically illustrates an operational flow of the apparatuses,methods, and computer program products of one exemplary aspect of thepresent disclosure directed to the identification of patterns in actualdata across a plurality of samples; and

FIG. 8 schematically illustrates actual, uncorrected displayed data, andaligned or re-aligned displayed data as corrected, according to oneaspect of the present disclosure.

DETAILED DESCRIPTION OF THE DISCLOSURE

The present disclosure will now be described more fully hereinafter withreference to exemplary embodiments thereof. These exemplary embodimentsare described so that this disclosure will be thorough and complete, andwill fully convey the scope of the disclosure to those skilled in theart. Indeed, the disclosure is embodied in many different forms andshould not be construed as limited to the embodiments set forth herein;rather, these embodiments are provided so that this disclosure willsatisfy applicable legal requirements.

The various aspects of the present disclosure mentioned above, as wellas many other aspects of the disclosure, are described in further detailherein. The apparatuses and methods associated with aspects of thepresent disclosure are exemplarily disclosed, in some instances, inconjunction with an appropriate analytical device which may, in someinstances, comprise a separator portion or separation portion (e.g., achromatograph) and/or a detector portion (e.g., a spectrometer). Oneskilled in the art will appreciate, however, that such disclosure is forexemplary purposes only to illustrate the implementation of variousaspects of the present disclosure. Particularly, the apparatuses andmethods associated with aspects of the present disclosure can be adaptedto any number of processes that are used to generate complex sets ofdata for each sample, over/across a plurality of samples, whetherbiological, chemical, or biochemical, in nature. For example, aspects ofthe present disclosure may be used with and applied to a variety ofdifferent analytical devices and processes including, but not limitedto: analytical devices including a separator portion (or “componentseparator” or “component separation” portion) comprising one of a liquidchromatograph (LC) and a gas chromatograph (GC); a cooperating detectorportion (or “mass spectrometer” portion) comprising one of a nuclearmagnetic resonance imaging (NMR) device; a mass spectrometer (MS); andan electrochemical array (EC); and/or combinations thereof. In thisregard, one skilled in the art will appreciate that the aspects of thepresent disclosure as disclosed herein are not limited to metabolomicsanalysis. For example, the aspects of the present disclosure asdisclosed herein can be implemented in other applications where there isa need to characterize or analyze small molecules present within asample or complex mixture, regardless of the origin of the sample orcomplex mixture. For instance, the aspects of the present disclosure asdisclosed herein can also be implemented in a bioprocess optimizationprocedure where the goal is to grow cells to produce drugs or additives,or in a drug metabolite profiling procedure where the goal is toidentify all metabolites that are the result of biotranformations of anadministered xenobiotic. As will be appreciated by one skilled in theart, these exemplary applications may be very different from ametabolomics analysis, where the goal is only to examine endogenousmetabolites. Some other non-limiting examples of other applicationscould include a quality assurance procedure for consumer productmanufacturing where the goal may be to objectively ensure that desiredproduct characteristics are met, in procedures where a large number ofsample components can give rise to a particular attribute, such as tasteor flavor (e.g., cheese, wine or beer), or scent/smell (e.g.,fragrances). One common theme thus exhibited by the aspects of thepresent disclosure as disclosed herein is that the small molecules inthe sample can be analyzed using the various apparatus and methodaspects disclosed herein.

FIG. 1 illustrates an example of a system according to one aspect of thepresent disclosure wherein the system is in communication with ananalytical device 110, such as a combination chromatograph (componentseparator/component separation)/mass spectrometer. One skilled in theart will appreciate, however, that the configurations of an analyticaldevice 110 presented herein are for exemplary purposes only, and are notintended to be limiting with respect to the scope of suitable andappropriate analytical devices that may also be applied under theprinciples disclosed herein As shown, a sample (whether biological,chemical, or biochemical, in nature) 100 may be introduced into theseparator portion/separation portion of the analytical device 110 andanalyzed using appropriate techniques, as applied through the detectorportion, that will be appreciated by those skilled in the art. Forexample, the components of a particular sample 100 may pass through acolumn associated with the separator portion/separation portion, atdifferent rates and exhibit different spectral responses (e.g.,associated with intensity as a function of retention time), as detectedby the detector portion, based upon their specific characteristics. Aswill be appreciated by one skilled in the art, the analytical device 110may generate a set of spectrometry data, corresponding to each sample100 and having three or more dimensions (e.g., quantifiable samplesproperties) associated therewith, wherein the data included in the dataset generally indicates the composition of the sample 100. In someaspects, the data set may comprise, for example, data for each samplerelated to retention time, sample or component (ion) mass, intensity, oreven sample indicia or identity. However, such data must first beappropriately analyzed in order to determine the sample composition.

In some instances, a three-dimensional data set for each of one or moresamples may be selected or otherwise designated for further analysis,with each dimension corresponding to a quantifiable sample property. Anexample of such a three-dimensional set of spectrometry data is showngenerally in FIG. 2, and may be plotted on a three-axis plot or graph,with the plot or graph including individual axes for a responseintensity element 220, a sample component mass element 210, and a timeelement 230 (particularly, in this example, the retention time or thetime that a particular component spends in the column of the separatorportion of the analytical device 110). That is, the data obtained for aparticular sample, in some aspects, includes a relationship between ionmass 210, retention time 230, and intensity 220, including intensity 220as a function of retention time 230 for a particular ion mass 210. Thelocation of data points in relation to the sample component mass axis210 may be indicative, for example, of the number of individualcomponent molecules within the sample 100 and the relative mass valuesfor such sample components. According to other aspects of the presentdisclosure, other analytical devices may be used to generate a three ormore dimensional set of analytical data corresponding to the sample 100.For example, the analytical device may include, but is not limited to:various combinations of a separator portion/separation portioncomprising one of a liquid chromatograph (LC) (positive or negativechannel) and a gas chromatograph (GC); and a cooperating detectorportion comprising one of a nuclear magnetic resonance imaging (NMR)device; a mass spectrometer (MS); and an electrochemical array (EC). Oneskilled in the art will appreciate that such complex three or moredimensional data sets may be generated by other appropriate analyticaldevices that may be in communication with components of aspects of thepresent disclosure as described in further detail herein.

One or more samples 100 may be taken individually from a well plate 120and/or from other types of sample containers and introduced individuallyinto the analytical device 110 for analysis and generation of thecorresponding three or more dimensional data set (see, e.g., FIG. 2).For example, individual samples 100 may be transferred from a well plate120 to the analytical device 110 via pipette, syringe, microfluidicpassageways defined by a test array, and/or other systems fortransferring samples in a laboratory environment. As disclosed herein,the nature of the samples may vary considerably, generally comprisingmixtures or complex mixtures including small molecules, wherein suchsamples may exemplarily include, but are not limited to: blood samples,urine samples, cell cultures, saliva samples, plant tissue and organs(e.g., leaves, roots, stems, flowers, etc.), plant extracts, culturemedia, membranes, cellular compartments/organelles, cerebral spinalfluid (CSF), milk, soda products, food products (e.g., yogurt,chocolate, juice), and/or other types of biological, chemical, and/orbiochemical samples in which the metabolites and/or chemical/molecularcomponents of interest may be present. Of these possible samples orsample types, one common aspect is that the selected sample includes aknown characteristic. This known characteristic may be, for example, atleast a general type or classification, a source, etc. Empirical data orother information associated with the known characteristic of the samplemay be implemented to determine, for example, one or more ions, smallmolecules or metabolites expected to be present in such a sample havingthat known characteristic. That is, such information associated with theknown characteristic provides a context to the sample and the dataobtained therefrom via the component separation and mass spectrometersystem, wherein the context provides an indicia at least as to a basiccomponent or constituent of the sample.

As shown in FIG. 1, aspects of the present disclosure may comprise anion data repository comprising, for example, a database (e.g., arelational database) stored at least in part, for example, as executableor accessible instructions in a memory or memory device 140 (i.e., acomputer-readable storage medium having computer-readable program codeportions stored therein), wherein the memory device 140 is incommunication with a processor or processor device 130 (e.g., a computerdevice implementing a processor) for selectively executing theinstructions/computer-readable program code portions in the memorydevice 140 to cause an apparatus to perform particular method stepsand/or functions. In some instances, the memory device 140 and/or theprocessor device 130 may be configured to be in communication, whetherdirectly or indirectly, with the analytical device 110 for receiving adata set (in some instances, a data set comprising three or moredimensions, wherein a data parameter such as sample indicia, sample orcomponent (ion) mass, retention time, and intensity/response mayrepresent any one of the dimensions of the data set), corresponding tothe sample 100, therefrom. That is, the dataset received by the memorydevice includes, for example, data indicating a relationship between ionmass, retention time, and intensity. In some particular instances, thedataset (for each of one or more samples 100) includes data indicatingintensity as a function of retention time for a particular ion mass. Theprocessor device 130 may be in communication with the analytical device110 via wire line (RS-232, and/or other types of wire connection) and/orwireless (such as, for example, RF, IR, or other wireless communication)techniques such that the database associated with the memory device140/processor device 130 (and/or in communication therewith) may receivethe data set from the analytical device 110 so as to be stored thereby.

Furthermore, the analytical device 110 may be in communication with oneor more processor devices 130 (and associated user interfaces and/ordisplays 150) via a wire line and/or wireless computer networkincluding, but not limited to: the Internet, local area networks (LAN),wide area networks (WAN), or other networking types and/or techniquesthat will be appreciated by one skilled in the art. The userinterface/display 150 may be used to receive user input and to conveyoutput such as, for example, displaying any or all of the communicationsinvolving the system, including the manipulations and analyses of sampledata disclosed herein, as will be understood and appreciated by oneskilled in the art. The database may be structured usingcommercially-available software, such as, for example, Oracle, Sybase,DB2, or other database software. As shown in FIG. 1, the processordevice 130 may be in communication with the user interface/display 150and the memory device 140 (such as a hard drive, memory chip, flashmemory, RAM module, ROM module, and/or other memory device 140) forstoring/administering the ion data repository/database, including thedata sets received from the analytical device 110, whether automatically(directly) or indirectly. In addition, the memory device 140 may also beused to store other received data or information involving the sample(s)or component(s) thereof in the ion data repository/database and/or dataotherwise manipulated by the processor device 130.

The processor device 130 may, in some aspects, be capable of convertingeach of the data sets, each including, for example, data indicating arelationship between various sample parameters such as ion mass,retention time, and intensity (see, e.g., FIG. 2, wherein the exemplarydata set is a three-dimensional data set) for each of the samples,received by the memory device 140, into at least one correspondingtwo-dimensional data set (see, e.g., FIG. 3). The at least onetwo-dimensional data set may comprise, for example, a two-dimensionalcomponent “profile” of a particular sample 100 at a particular point 235(FIG. 2) along one of the three axes of the three-dimensional data set.The particular point 235 along one of the three axes may be, forexample, a particular selected sample component mass along the samplecomponent mass axis 210. Once that particular sample component mass isselected, the resulting “slice” of the three-dimensional data setbecomes the two-dimensional profile plot for the sample. That is, theresulting profile (also referred to herein as a “profile plot” as shownin FIGS. 3 and 4) illustrates that particular sample component massdetected (and the intensity of that detection) as a function of timemeasured from a zero point, the zero point corresponding to when thesample 100 is injected and/or otherwise introduced into the analyticaldevice 110). For example, the processor device 130 may be configured toproduce a detection intensity/response versus/as a function of samplecomponent (retention) time two-dimensional profile of the sample forthat given or selected sample component mass point 235 (see FIGS. 3 and4, for example). The “x” axis in FIG. 2 (or (retention) time axis 230,for example) may further, in some instances, be characterized as aretention index and/or a retention time. Thus, the processor device 130may be further capable of parsing each of the three (or more)dimensional data sets, for each of the plurality of samples, into one ormore individual two-dimensional (i.e., intensity/response versus samplecomponent retention time profile) profiles corresponding to at least oneparticular (selected) sample component mass point (element 235, forexample) so as to convert each three (or more) dimensional data set (ofFIG. 2, for example) into at least one corresponding two-dimensionaldata set of a selected sample component (having a profile or profileplot shown, for example, in FIGS. 3 and 4) that may further be plottedas an response intensity 220 of the corresponding sample component massversus a sample component retention time 230, and displayed on the userinterface/display 150, as desired. One skilled in the art willappreciate that any amount of two-dimensional data sets or profile plotsmay be formed or obtained from any three or more dimensional data setsby selecting two different sample parameters at a selected particularvalue of a third sample parameter, and then plotting the two differentsample parameters against each other in a two-dimensional plot.

According to some aspects, the processor device 130 may be configured toselectively execute the executable instructions/computer-readableprogram code portions stored by the memory device 140, if necessary, incooperation with the ion data repository/database also stored by thememory device 140, so as to accomplish, for instance, theidentification, quantification, representation, curation, and/or otheranalysis of a selected sample component (i.e., a metabolite, molecule,or ion, or portion thereof) in each of the plurality of samples, fromthe two-dimensional data set representing the respective sample amongthe plurality of samples. In doing so, the sample component of interestfrom the sample to be analyzed is first determined from at least oneknown characteristic associated with the sample. The at least one knowncharacteristic associated with the sample may include, for example, atleast a general type or classification, a source, etc. In some aspects,the at least one known characteristic may involve a particular nature ofthe sample, wherein the particular nature of the sample may varyconsiderably, from generally comprising mixtures or complex mixturesincluding small molecules, to particularly and exemplarily including,without limitation: blood samples, urine samples, cell cultures, salivasamples, plant tissue and organs (e.g., leaves, roots, stems, flowers,etc.), plant extracts, culture media, membranes, cellularcompartments/organelles, cerebral spinal fluid (CSF), milk, sodaproducts, food products (e.g., yogurt, chocolate, juice), and/or othertypes of biological, chemical, and/or biochemical samples. The at leastone known characteristic, in particular aspects, indicates whichmetabolites and/or chemical/molecular components of interest may bepresent in that sample. That is, in addition to data regarding discreteparticular ions, the ion data repository/database may also includeempirical data or other information associated with the knowncharacteristic of the sample.

Accordingly, upon identifying the at least one known characteristic ofthe sample or receiving the at least one known characteristic as aninput via the user interface/display 150, the processor 130 may beconfigured to execute computer-readable program code portions stored bythe memory device 140 for implementing the empirical data and otherinformation to correlate the one or more known characteristics with oneor more particular ions, small molecules or metabolites expected to bepresent in such a sample having that known characteristic. That is, insome aspects, such information and empirical data associated with theone or more known characteristics provides a context to the sample andthe data obtained therefrom, wherein the context provides an indicium atleast as to a basic component or constituent of the sample, or whererelevant data may be located within the ion data repository/database. Inturn, the particular identifying data associated with the indicium ofthe basic component or constituent, or information location within theion data repository/database, further indicates candidate ions,compounds and components that may be present or are expected orpredicted to be present in the sample under analysis. That is, inparticular aspects, comparing the known characteristic to empirical dataincluded in the ion data repository, wherein the empirical data includesrelational information between known characteristics and certain ions,allows the determination therefrom of the one or more ions correspondingto the known characteristic(s). In particular aspects of the disclosure,the selecting, based on the known characteristic, of one or more ionsfrom the ion data repository expected to be included in the sample maybe facilitated by more extensive information and empirical data receivedand housed within the ion data repository/database, wherein any“learning” by the processor 130 represents efficiencies and accuraciesgained from additional correlative information.

As such, one aspect of the present disclosure involves the inclusion ofdata and information regarding the analysis of all samples into the iondata repository/database such that this “historical data” can be used tosupplement the predictions and analyses for future analyzed samples.That is, more robust data and information included in the ion datarepository/database, wherein such data and information in continuallysupplemented by additional sample analyses and inclusion of externallysourced information, could lead to more accurate designations of one ormore ions or other components that are expected to be present in thedata for a particular sample, as well as more efficient comparison ofdata for the particular sample to data for the one or more expected ionsselected from the ion data repository/database to identify any of theone or more ions that is actually present in the sample in averification/curation process. In particular aspects, the robust dataand information in the ion repository/database does not necessarily needto be all correlative, but may also be any or all of inconsistent,contrary, or otherwise noncontributory toward a particular conclusion.That is “truths” as well as “untruths” or “non-truths” may all benecessarily included in the ion data repository/database to provide acomplete and robust ion data repository/database for the purposesdetailed herein.

In some aspects, to facilitate the analysis of a sample having knowncharacteristics, it may also be helpful to have data associated with astandard or reference included in the analysis. Accordingly, in someaspects, a reference ion (though a reference ion is specified here, oneskilled in the art will appreciate that such a reference ion may beinterchangeable with a reference compound, reference sample component,or any other reference or standard suitable for data analysis in asimilar manner as the sample), may be implemented in the componentseparation and mass spectrometer system in a separate run from thesample or contemporaneously with the sample, or the reference ion canotherwise be included in the sample itself in a single run through thecomponent separation and mass spectrometer system.

According to aspects of the present disclosure, the processor 130 may beconfigured to execute computer-readable program code portions stored bythe memory device 140 for analyzing data obtained from the componentseparation and mass spectrometer system for a reference ion (whetherthat reference ion is included in a separate run from the sample, runcontemporaneously with the sample, or otherwise included in the sampleand run together) to determine one or more relationships within thedata, such as between reference ion mass, retention time, and intensity(see, e.g., FIG. 5, block 600). Such one or more relationships, in someaspects, particularly include intensity as a function of retention timefor the reference ion mass. In such aspects, the reference ion has orexhibits an intensity maxima/maximum at a characteristic retention timefor the reference ion mass. In this regard, one skilled in the art willappreciate that the one or more relationships, in other aspects, mayparticularly include, for example, intensity as a function of the ionmass for a selected retention time. Accordingly, further discussionherein referring to intensity as a function of retention time for aselected ion mass will be similarly applicable to intensity as afunction of the ion mass for a selected retention time. The analysis ofthe reference ion (or reference sample) may, for example, provide acontemporaneous reference or indictor by which to assess the analysis ofthe sample(s) otherwise analyzed as disclosed herein.

Upon completion of the analysis, the processor device 130 may beconfigured to execute computer-readable program code portions stored bythe memory device 140 for adding the analyzed data for the reference ionto the ion data repository/database, if data for the reference ion isnot already included in the ion data repository (see, e.g., FIG. 5,block 610). In such instances, the data for each of the ions in the iondata repository, including data for the reference ion, is stored suchthat each ion has, for example, data exhibiting an intensitymaxima/maximum within a range of characteristic retention times for acharacteristic ion mass. That is, when a reference ion is run throughthe component separation and mass spectrometer system, a characteristicion mass for that reference ion will be expected or predicted to exhibita particular intensity maxima/maximum within an expected range ofretention times.

If data for the reference ion was previously included in the ion datarepository/database, the range of characteristic retention times of thereference ion in the ion data repository is modified according to thecharacteristic retention time of the determined intensity maxima for thereference ion (see, e.g., FIG. 5, block 620) from the analysis of thereference ion. That is, if data for the reference ion was previouslyincluded in the ion data repository and the determined intensity maximais within the range of characteristic retention times, the range ofcharacteristic retention times for the reference ion in the ion datarepository/database is reduced accordingly (i.e., reduction of the rangeresulting from increase certainly of the expected retention time for thecharacteristic ion mass) based on a direct or indirect factor (e.g.,running average, weighted average, statistical certainty, etc.).However, if the determined intensity maxima is outside the range ofcharacteristic retention times, the range of characteristic retentiontimes may be appropriately increased (i.e., if the determined intensitymaxima is not significantly or materially outside the range). In otherinstances, the determined intensity maxima may not be used to affect therange of characteristic retention times, may otherwise be added to theempirical data/other information in the ion data repository/database inassociation with the reference ion, or the data including the determinedintensity maxima may be used to determine whether any data deviationfactors in the component separation and mass spectrometer system requirefurther consideration. Such further consideration may include, forexample, determining whether there has been any drift or shift in thecomponent separation and mass spectrometer system (e.g., due to columnaging), or determining whether the component separation and massspectrometer system is being consistent between sequential runs or runswith similar samples. As previously indicated, these steps/actions arelikewise similarly applicable if the particular data relationship ofinterest includes intensity as a function of the ion mass for a selectedretention time. In such instances, the affected parameter in the iondata repository/database will be the range of characteristic ion massesfor the reference ion or the particular selected ion/ion of interest.

In some aspects, the processor device 130 may be configured to executecomputer-readable program code portions stored by the memory device 140for subsequently analyzing the data obtained from the componentseparation and mass spectrometer system for the sample having the knowncharacteristic to determine one or more relationships within the datasuch as, for example, a relationship between sample ion mass, retentiontime, and intensity, wherein such a relationship may particularlyinclude intensity as a function of retention time for a selected sampleion mass. An ion present in the data for the sample may then be selected(for example, by a user from the display of the relationship ofintensity as a function of retention time for the selected sample ionmass on the user interface/display 150), wherein the selected ion has anintensity maxima/maximum (e.g., an ion peak) at a characteristicretention time for the selected sample ion mass.

That is, in some aspects, the processor device 130 may be configured toexecute computer-readable program code portions stored by the memorydevice 140 for selecting an intensity peak/maxima/maximum (see, e.g.,element 225 in FIG. 4) or intensity peak/maxima/maximum arrangement(see, e.g., element 225 in FIG. 3) generally present with sufficientquality in the two-dimensional data set of metabolomics data for thesample (i.e., “at least one identifying peak”). As previously disclosed,such two-dimensional data sets are determined from respective three ormore dimensional data sets of metabolomics data for the sample,generally by selecting or otherwise designating two desireddimensions/axes with each dimension/axis corresponding to a differentsample parameter, and selecting a particular value (e.g., retention timeor sample ion mass) with respect to another one of the dimensions/axesof the three or more dimensional data set in relation to the twodifferent sample parameters forming the two dimensions/axes. One skilledin the art will appreciate, however, that the ion or component of thesample to be analyzed may, in some instances, be selected from the threeor more dimensional data set, if necessary or desired, and that suchselection of the ion or component of the sample to be analyzed may befurther refined upon analysis of the two-dimensional data setcorresponding thereto. In some instances, the selection of the ion orcomponent of the sample to be analyzed may be facilitated, for example,by analyzing a graphical representation of the three or more dimensionaldata set(s) (i.e., via user interface or display 150, which maycomprise, for example, a display device, personal computer, and/or otherelectronic/computer device having a display for graphical representationof data), and the selection may involve, for instance, evaluating theapparent response/intensity of that ion or component of the sample inthe respective two-dimensional and/or three or more dimensional datasets, to determine the intensity peak or intensity peak arrangement 225(i.e., “at least one identifying peak”) to be user-selected for furtheranalysis.

In this manner, the processor device 130 may also be configured, forinstance, to examine intensity peak/maxima/maximum or intensitypeak/maxima/maximum arrangement data that is sufficiently discerniblefrom background noise or other undesirable data artifacts (i.e., ofsuitable quality), in order to reduce variances and provide a morestatistically significant analysis upon determining the selectedintensity peak or intensity peak arrangement 225 (i.e., “at least oneidentifying peak”). As referred to herein, in some instances, an“intensity peak arrangement” or combination of intensity peaks/maxima225 may comprise, for example, a “main peak” 225A and at least one“sub-peak” 225B, 225C, 225D following on the retention time axis (see,e.g., FIG. 3). Such an “intensity peak/maxima/maximum arrangement” orcombination of intensity peaks 225 may result, for example, frominstances of co-elution in high throughput processing of samples throughthe analytical device(s). With such high throughput processing, theintensity peaks representing the various metabolites may not be detectedby the analytical device(s) in such a manner as to appear “wellseparated” (i.e., “well resolved”) from each other in the resultingdata, and may thus appear as groups of intensity peaks as shown, forexample, in FIG. 3. In some cases, the at least one sub-peak 225B, 225C,225D may have a lesser intensity/response than the main peak 225A,though not necessarily always evident. In other cases, one or more ofthe at least one sub-peak may be evident prior to the main peak 225A onthe retention time axis 230. In instances where a metabolite/ion isdistinct from others in the sample (i.e., “well separated” or“well-resolved”), or in instances where the analytical device(s) receivethe samples under favorable conditions, the intensity peaks representingthe various metabolites may be detected by the analytical device(s) insuch a manner as to appear “well-separated/well-resolved” from eachother in the resulting data, and may thus appear as a separate,distinct, and/or discrete intensity peak/maxima/maximum as shown, forexample, in FIG. 4.

In one aspect, in order to determine the selected intensity peak orintensity peak arrangement, the processor device 130 may be configuredto first identify a plurality of candidate intensity peaks or intensitypeak arrangements in the two-dimensional data set for the sample,wherein, for example, the candidate intensity peak or intensity peakarrangement with the lowest standard deviation (i.e., the best dataquality of the main peak 225A across the samples) may be selected as theselected intensity/ion peak or intensity/ion arrangement 225. However,one skilled in the art will appreciate that the selected intensity peakor intensity peak arrangement may be determined in other manners. Forexample, upon comparing the candidate intensity peak arrangements acrossthe two-dimensional data set for the samples, one of the candidateintensity peaks or intensity peak arrangements evident across thetwo-dimensional data set, and corresponding to a recognized compound,metabolite, ion, or component or portion thereof in an the associatedion data repository/database of such compounds, metabolites, ions, orcomponents or portions thereof, may be selected via the userinterface/display 150 as the selected intensity/ion peak or intensitypeak arrangement. More particularly, for instance, the candidateintensity peaks or intensity peak arrangements across thetwo-dimensional data set may be compared with mass spectra included inthe ion data repository/database housing recognized or otherwise knowncompounds (i.e., using a library or database matching process), followedwith subjective curation or resolution of the matching process, ifnecessary. In such an instance, one of the candidate intensity peaks orintensity peak arrangements matched with, corresponding to, or bestcorrelated with, the recognized or known compound (e.g., by comparisonof quantitative mass) may be selected as the selected intensity/ion peakor intensity peak arrangement 225 as shown, for example, in FIGS. 3 and4, and may facilitate or otherwise promote consistent analysis betweensamples.

In particular aspects, the processor device 130 may further beconfigured to execute instructions/computer readable program codeportions so as to identify a particular compound or sample component(e.g., a metabolite) associated with the selected and analyzed intensitypeak or intensity peak arrangement 225). The particular compound/samplecomponent may be “known named” and/or “known, but unnamed”chemicals/compounds. That is, for example, the identified particularcompound/sample component may correspond to a metabolite having achemical nomenclature or to a “known, but unnamed” metabolite which hasbeen previously identified, but not yet assigned a chemical name and/orclassification. One skilled in the art will appreciate that suchcompound identification procedures may be accomplished in many differentmanners with respect to the selected intensity peak/intensity peakarrangement 225 and/or the corresponding two-dimensional orthree-dimensional data set. For example, some compound identificationprocedures are disclosed in U.S. Pat. No. 7,433,787 (System, Method, andComputer Program Product Using a Database in a Computing System toCompile and Compare Metabolomic Data Obtained From a Plurality ofSamples); U.S. Pat. No. 7,561,975 (System, Method, and Computer ProgramProduct for Analyzing Spectrometry Data to Identify and QuantifyIndividual Components in a Sample); and U.S. Pat. No. 7,949,475 (Systemand Method for Analyzing Metabolomic Data), all assigned to Metabolon,Inc., which is also the assignee of the present application. To theextent that such compound identification procedures are relevant to thedisclosure herein, such compound identification procedures disclosed byU.S. Pat. Nos. 7,433,787; 7,561,975; and 7,949,475 are incorporatedherein by reference, and not otherwise discussed in detail herein forthe sake of brevity.

The processor device 130 may be further configured to align the selectedintensity peak or intensity peak arrangement 225 evident in thetwo-dimensional data set for the sample in conjunction with thecollection of data associated therewith from the component separationand mass spectroscopy system, prior to further analysis of the data.More particularly, various compounds (including metabolites) may move atsomewhat different rates during a separation process, from one sample toanother, so that it may not be entirely clear which peaks or peakarrangements (corresponding to eluted or co-eluted compounds, forexample) should be considered as corresponding to a known compoundwithin the sample. As such, the processor device 130 may be configuredto execute instructions/computer readable program code portions toimplement an intensity peak/peak arrangement alignment correction methodfor the selected intensity peak or peak arrangement in thetwo-dimensional data set for the sample. For example, one such methodinvolves spiking known compounds (e.g., a reference sample or referenceion) into each sample, wherein the known compounds are characterized byknown retention times (RT) in spectrometry analysis. The set of “spiked”compounds matches a fixed retention index (RI) value to the shifting RT.The “spiked” compounds thus provide an internal standard (IS) that maybe used to align data from the sample between the particular study andthe ion data repository/database (i.e., chemical library). One skilledin the art will appreciate, however, that many different methods may beused to perform the intensity peak/peak arrangement alignment for theselected intensity peak or peak arrangement for the sample, within thespirit and scope of the present disclosure, and that the examplepresented herein in this respect is not intended to be limiting in anymanner.

If the selected ion is related to or otherwise associated with the knowncharacteristic or the reference ion, the previous analysis of the knowncharacteristic or the reference ion may then serve as a basis for theanalysis of data for the sample. For example, the direction provided bythe known characteristic of the sample or the location or context of thedata and information for the reference ion within the ion datarepository/database may be indicative of or lead to the determination ofthe one or more ions expected to be present in the sample. Once theparticular ion from the sample data set is selected, for example, by auser via the user interface/display 150 (see, e.g., FIG. 5, block 630),the processor device 130 may be configured to execute computer-readableprogram code portions stored by the memory device 140 for thencomparing, on a display associated with the user interface, dataobtained from the component separation and mass spectrometer system forthe sample to data for each of the one or more ions selected from theion data repository to determine whether any of the one or more ions ispresent in the sample (see, e.g., FIG. 5, block 640). The processordevice 130 may be further configured to execute computer-readableprogram code portions stored by the memory device 140 for modifying, viathe user interface, the range of characteristic retention times of eachof the one or more ions determined to be present in the sample, in thedata repository, according to the characteristic retention time of theintensity maxima for a respective one of the one or more ions determinedto be present in the sample (see, e.g., FIG. 5, block 650).

In some aspects, the determination of the one or more ions expected tobe present in the sample may include querying the ion datarepository/database via the user interface/display 150/processor 130 toselect the one or more ions therefrom based upon a retention time of anintensity maxima/maximum of the selected ion (i.e., a selected ion peak)from the data for the sample in relation to the range of characteristicretention times of the intensity maxima/maximum of the one or more ionsin the ion data repository/database. That is, in some aspects, thedetermination of the one or more ions expected to be present in thesample may be accomplished by comparing the intensity maxima/ion peakselected from the sample data to intensity maxima/ion peaks in the iondata repository/database having characteristic retention time rangesoverlapping with the retention time of the intensity maxima/ion peakselected from the sample data.

In other aspects, where the sample is one of a plurality of samples in asample run or batch, selecting the one or more ions from the ion datarepository expected to be included in the sample, based on the knowncharacteristic, comprises selecting the one or more ions from the iondata repository determined to be present in a first one of the pluralityof samples for comparing to the data for a remainder of the samples inthe sample run. That is, for a multi-sample run or batch introduced tothe component separation and mass spectrometer system, the one or moreions determined as expected/predicted to be included in the sample mayserve as a context for the one or more ions expected to be included inthe data for the remainder of the samples in that run/batch. In suchinstances, the data obtained from the multi-sample run/batch may beuseful for checking or verifying consistency or drift or shift of thecomponent separation and mass spectrometer system over the multiplesample runs.

In still other aspects, the determination of whether any of the one ormore ions from the ion data repository expected to be included in thesample are actually present in the sample may be visually facilitated inthe verification/curation process, for example, via the userinterface/display 150. That is, the step of comparing data for thesample to data for the one or more ions selected from the ion datarepository, in some instances, comprises comparing a two dimensionalplot of intensity as a function of retention time for the dataassociated with the sample to a two dimensional plot of intensity as afunction of retention time for the data associated with each of the oneor more ions selected from the ion data repository, via the userinterface/display 150, so as to provide a visual indication of intensitymaxima therebetween for determining whether any of the one or more ionsis present in the sample (see, e.g., FIG. 6, element 900).

Once the one or more ions expected to be present in the sample aredetermined, and any of the one or more candidate ions are identified orverified (curated) to be present in the sample, the data associated withthe selected (identified/verified) ion is included in the ion datarepository/database as historic/empirical data or other informationassociated with the identified/verified ion. That is, in particularaspects, upon completion of data analysis for a sample, empirical datafrom the analysis and associated with the sample is added to the iondata repository/database in relation to the any of the one or more ionsdetermined to be present in the sample. In other instances, for example,the range of characteristic retention times of each of the one or moreions determined to be present in the sample, in the data repository, maybe modified via the user interface/display 150 according to thecharacteristic retention time of the intensity maxima for a respectiveone of the one or more ions determined to be present in the sample.Further, in some aspects, the range of characteristic retention times ofthe ion in the ion data repository, identified to correspond to theselected ion, may also be modified according to the characteristicretention time of the intensity maxima for the selected ion once theselected ion is identified. More particularly, if the determinedintensity maxima/maximum for the identified ion is within the range ofcharacteristic retention times, the range of characteristic retentiontimes for the identified ion in the ion data repository/database isreduced accordingly (i.e., reduction of the range resulting fromincrease certainly of the expected retention time for the characteristicion mass) based on a direct or indirect factor (e.g., running average,weighted average, statistical certainty, etc.).

In another aspect, in addition to the identification(curation/verification) of compounds, ions or other sample components,the processor 130 may be configured to execute computer-readable programcode portions stored by the memory device 140 for distinguishing betweenthose compounds/ions/sample components that are present and biologicallyor statistically relevant in the sample(s) and those that are anartifact (e.g., either contamination of/within the sample or amanifestation of measurement noise), or are otherwise sparse orinsignificant within or across the plurality of samples or sample set(i.e., not present in sufficient quantity to inform aggregate analysisacross a sample set). This capability leverages the identification(curation/verification) capability disclosed herein and the comparisonof analysis results from actual samples to analysis results from controlsamples, which may further increase the speed of the datacuration/verification process disclosed herein.

For example, in some instances, artifacts may be detected by acomparison between data for actual samples and data for a consistent,previously-characterized sample (e.g., an “anchor sample”). In someparticular instances, the consistent, previously characterized samplemay comprise water (e.g., a water blank). Such a comparison is premisedon, for example, that a compound/ion/sample component detected in theconsistent, previously-characterized sample at a level (e.g. intensity)similar to the actual sample(s), or otherwise within a specifiedthreshold in relation thereto, that compound/ion/sample component isflagged as likely being and artifact within the sample(s) andsubsequently excluded from statistical analysis of the sample data.

More particularly, in some aspects, data obtained from the componentseparation and mass spectrometer system for an anchor sample, whereinthe anchor sample is defined as a consistent, previously-characterizedsample, is analyzed to determine a component ion of the anchor sample.For that component ion, a relationship between component ion mass,retention time, and intensity, including intensity as a function ofretention time for the component ion mass, is also determined. Thecomponent ion will have and demonstrate an intensity maxima/maximum at acharacteristic component ion retention time for the component ion mass.On the basis of the component ion mass being substantially equal to thecharacteristic ion mass of one of the one or more ions determined to bein the sample, the intensity maxima/maximum for the component ion at thecharacteristic component ion retention time, is compared to theintensity maxima/maximum for the one of the one or more ions determinedto be in the sample at the characteristic retention time. As such, ifthe intensity maxima/maximum for the component ion and the one of theone or more ions determined to be in the sample are substantiallysimilar, then the one of the one or more ions determined to be in thesample is designated as an artifact ion in the sample. The artifact ioncan then be flagged or otherwise indicated as being excluded fromfurther analysis of the sample data.

A sparse compound/ion/sample component may be detected by determiningthe occurrence/presence of the compound/ion/sample component withinsample(s) across the sample set. For example, if the compound/ion/samplecomponent is only detected in a small percentage of the samples or undera predetermined threshold of samples within the sample set, thecompound/ion/sample component is excluded from further analysis sincethat the compound/ion/sample component will not contribute positively tothe data analysis. In other instances, for example, run-day-based ordetector sensitivity trend-based factors associated with the detectionof the compound/ion/sample component may cause the compound/ion/samplecomponent to be designated for more thorough analysis, but likely forexclusion from the data analysis.

More particularly, in instances where the sample comprises a pluralityof samples in a sample run, the plurality of samples in the sample runis analyzed to determine a presence of one of the one or more ions fromthe ion data repository determined to be present in a first one of theplurality of samples, across the plurality of samples. As such, if athreshold quantity of the samples in the plurality of samples does notinclude the one of the one or more ions from the ion data repositorydetermined to be present in the first one of the plurality of samples,then the one of the one or more ions determined to be present in thefirst one of the plurality of samples is designated as sparse ion in theplurality of samples, and excluded from further analysis of the sampledata.

Fundamental to the data curation/verification disclosed herein is thatthe intensity peak/maxima/maximum of the analyzed sample(s) must bematched with the correct identifying compound/ion if further dataanalysis according to the present disclosure is to be useful/effective.As such, the processor 130 may be configured to executecomputer-readable program code portions stored by the memory device 140for performing a real time error correction functionality in instanceswhere moderate, systemic deviations from the expected/predicted location(e.g., within a particular range of retention times) of an intensitypeak/maxima/maximum are identified and corrected to provide increasedaccuracy of the analysis results.

For example, if there is shift/drift/or other systemic error that is notaddressed in the apparatuses, methods, and computer program productsdisclosed herein, such issues can be approached by: 1) widening theconfidence intervals of the predictions/expectations (i.e., expand therange of expected/predicted retention times), or 2) an iterative updateapproach. Aspects of the present disclosure implement the secondapproach since any deviations within the data tend to be systemic (e.g.samples run consecutively tend to demonstrate similar retention timesfor a given compound/ion/sample component). As such, it may be moreeffective to first identify any detected ion intensity peaks/maxima, andthen iteratively update or modify the predictions/expectations ofretention times for the ion peaks/maxima with the new data to conform toany unexpected shift or drift of the sample data.

More particularly, in instances where the sample comprises a pluralityof samples in a sample run, the data obtained from the componentseparation and mass spectrometer system for each sample is analyzed todetermine a relationship between sample ion mass, retention time, andintensity, including intensity as a function of retention time for aselected sample ion mass, wherein the selected sample ion mass isselected via the user interface/display 150 (see, e.g., FIG. 7, element700). The intensity is then analyzed as the function of the retentiontime for the selected sample ion mass for each of the samples, acrossthe plurality of samples, to identify an intensity maxima/maximum withina predicted range of retention times for each sample, wherein thepredicted range of retention times includes an expected intensitymaxima/maximum retention time therein for the selected sample ion mass(see, e.g., FIG. 7, element 710). For each sample, an actual retentiontime of the intensity maxima/maximum in relation to the expectedintensity maxima/maximum retention time is identified (see, e.g., FIG.7, element 720), and a determination is made as to whether the actualretention times of the intensity maxima/maximum of two or moreconsecutive samples of the plurality of samples in the sample rundemonstrate an identifiable pattern with respect to the expectedintensity maxima/maximum retention time (see, e.g., FIG. 7, element730).

If a pattern is identifiable in the sample data, the identifiablepattern of the actual retention times of the intensity maxima/maximum ofthe two or more consecutive samples, with respect to the expectedintensity maxima/maximum retention time, comprises a shift wherein theactual retention times of the intensity maxima/maximum are substantiallyconsistently offset from the expected intensity maxima/maximum retentiontime, or a drift wherein the actual retention times of the intensitymaxima/maximum are offset by a non-constant function from the expectedintensity maxima/maximum retention time. In general, the offset of theactual retention time of the intensity maxima/maximum of each of theplurality of samples in the sample run are corrected according to theidentifiable pattern.

In instances where the identifiable pattern of the actual retentiontimes of the intensity maxima of the two or more consecutive samples,with respect to the expected intensity maxima retention time,demonstrates an offset from the expected intensity maxima retention timewhich differs between two subsets of two or more consecutive samples inthe sample run, the offset of the actual retention times of theintensity maxima of each of the plurality of samples in the sample runmay be corrected according to the identifiable pattern of one of the twosubsets having a majority of the samples in the sample run.

In another aspect, the data curation/verification procedure associatedwith the apparatuses, methods, and computer program products disclosedherein allows the sample data obtained from the component separation andmass spectrometer system to be expediently analyzed by the processor 130configured to execute computer-readable program code portions stored bythe memory device 140 data. In instances where the data from theanalysis indicates systemic issues with the component separation andmass spectrometer system or other sample processing issues, thesample(s) must be re-run with properly operable instrumentation in orderto obtain valid and appropriate data. The expediency of the datacuration/verification process thus allows the collected data todetermine indications of issues with the component separation and massspectrometer system or other sample processing issues as soon as theanalysis data is received from the CS/MS system. As a result, anyrequired data re-runs can be ordered promptly (after addressing anyissues with the CS/MS system) and there may also be cost savings interms of preventing labor from being expended on data which wouldeventually be discarded, in any instance. This process also decreasesthe time required for addressing systemic errors, faults or issues inthe CS/MS system to be identified and corrected, thereby leading tofewer samples processed therethrough which may be required to be re-run.

More particularly, in regard to the data curation/verification processdisclosed herein, if comparing data obtained from the componentseparation and mass spectrometer system for the sample to data for eachof the one or more ions selected from the ion data repository todetermine whether any of the one or more ions is present in the sample,results in none of the one or more ions being present in the sample,then an instrument error associated with the component separation andmass spectrometer system can be resolved and the sample re-run throughthe component separation and mass spectrometer system in order to obtainreplacement data for the sample(s).

The data curation/verification process disclosed herein interfaces witha user by way of the user interface/display 150. As also previouslyaddressed, the disclosed process displays each of the one or more ionsfrom the ion data repository expected to be included in the sample whichincludes an intensity peak/maxima/maximum which falls within anexpected/predicted retention time range of that compound/ion/samplecomponent. However, a conventional singular visualization as a functionof retention index or as a function of retention time may be prone todrift, shift, run-day affects, and other issues which may contribute tomisalignment of data between samples, which makes manual curation moretime intensive and difficult, for example, from a labor anddecision-making standpoint. As shown, for example, in FIG. 8, aspects ofthe present disclosure provide a visualization, via the userinterface/display 150, of possible intensity peaks/maxima across allsamples, including the difference between each of the one or more ionsfrom the ion data repository expected to be included in the sample whichincludes an intensity peak/maxima/maximum which falls within anexpected/predicted retention time range of that compound/ion/samplecomponent, and the actual intensity as a function of retention time plot(e.g., ΔRT) for the sample(s). The correction of the actual sample(s)data according to the identifiable pattern (e.g., drift, shift, etc.) aspreviously discussed results in an alignment or re-alignment of theactual sample(s) data separately of defects found in the pure (ascollected) data representations of the intensity peaks/maxima (see,e.g., FIG. 8, element 1000 for the actual, uncorrected displayed dataand element 1100 for the aligned or re-aligned displayed data ascorrected herein for drift). As a result, the visualization facilitatesmanual curation by allowing a user to more quickly resolvecompounds/ions (e.g., from a labor and decision-making standpoint). Moreparticularly, the processor 130 may be configured to executecomputer-readable program code portions stored by the memory device 140for displaying, on the display 150 associated with the user interface,the corrected offset of the actual retention time of the intensitymaxima/maximum of each of the plurality of samples in the sample runaccording to the identifiable pattern to provide a visualization of thecorrected actual retention time of the intensity maxima of each of theplurality of samples across the plurality of samples in the sample run.

Aspects of the present disclosure also provide methods of analyzingmetabolomics data, as shown generally in the operational flow diagram ofFIG. 5, and as previously discussed herein. In addition to providingappropriate apparatuses and methods, aspects of the present disclosuremay also provide associated computer program products for performing thefunctions/operations/steps disclosed above, in the form of, for example,a non-transitory computer-readable storage medium (i.e., memory device140) having particular computer-readable program code portions storedtherein by the medium that, in response to execution by the processordevice 130, cause the apparatus to at least perform the steps disclosedherein. In this regard, FIG. 5 is an operational flow diagram associatedwith particular methods, apparatuses and computer program productsaccording to particular aspects of the present disclosure. It will beunderstood that each block or step of the operational flow diagram orcombinations of blocks in the operational flow diagram can beimplemented by appropriate computer program instructions executed by theprocessor device 130. These computer program instructions may be loadedonto a computer device or other programmable apparatus for executing thefunctions specified in the operational flow diagram otherwise associatedwith the method(s) disclosed herein. These computer program instructionsmay also be stored in a computer-readable memory (i.e., memory device140), so as to be accessible by a computer device or other programmableapparatus in a particular manner, such that the executable instructionsstored in the computer-readable memory may produce or facilitate theoperation of an article of manufacture capable of directing or otherwiseexecuting the instructions which implement the functions specified inthe operational flow diagram otherwise associated with the method(s)disclosed herein. The computer program instructions may also be loadedonto a computer device or other programmable apparatus to cause a seriesof operational steps to be performed on the computer device or otherprogrammable apparatus to produce a computer-implemented process suchthat the instructions executed by the computer device or otherprogrammable apparatus provide or otherwise direct appropriate steps forimplementing the functions/steps specified in the operational flowdiagram otherwise associated with the method(s) disclosed herein. Itwill also be understood that each step of the operational flow diagram,or combinations of steps in the operational flow diagram, can beimplemented by special purpose hardware-based computer systems whichperform the specified functions or steps, or combinations of specialpurpose hardware and computer instructions (software).

Many modifications and other aspects of the disclosure set forth hereinwill come to mind to one skilled in the art to which this disclosurepertain having the benefit of the teachings presented in the foregoingdescriptions and the associated drawings. For example, in some aspects,the improved apparatus, method, and computer program product, addressingthe technical issues and limitations associated with conventionalmetabolomic data analysis systems as identified herein, may facilitatescalability of the data curation/verification process disclosed herein.That is, the improved apparatus, method, and computer program productdisclosed herein increases the speed of the data curation/verificationprocess, wherein refinement thereof may result in the realization ofcuration/verification speed by several orders of magnitude over priorart technology, for example by processing data for up to 20K samples ata time with a single station. Such a single station capacity may, inturn, be scaled to multiple stations (e.g., computational units) withsimilar capacity, which will allow curation/verification data sets ofsignificant size to be expediently processed.

In another example, the methods, apparatuses and computer programproducts according to particular aspects of the present disclosure arepremised upon certain inputs or drivers or the conditions of such inputsor drivers, including:

-   -   The component separation and mass spectrometer system: The        models/software/algorithms implemented in the apparatuses,        methods, and computer program products of the present disclosure        may respond differently depending on the        state/behavior/condition of the component separation and mass        spectrometer system. The component separation and mass        spectrometer system may operate in distinct modes        (platforms/arms) which may vary based on the cleanliness of the        instrument, various environmental statuses (e.g., temperature,        humidity, etc.), age of the columns, pressure applied to the        columns, etc. The apparatuses, methods, and computer program        products of the present disclosure integrate data based on the        observed behavior of certain standards (e.g., endogenous        compounds), which then drive the process for other        compounds/ions in the ion data repository.    -   The Ion Data Repository: In this context, the ion data        repository includes, for example, data regarding a collection of        compounds/ions, their known general parameters, and fundamental        presence, which have been observed on each arm/platform of the        component separation and mass spectrometer system. In one        particular example, glucose has been observed in blood samples        when running platform A, wherein this observation is included in        the ion data repository among known compounds/ions. Further data        about the observed state of glucose is aggregated and included        in the ion data repository (e.g., ion mass value/range,        retention time/range, etc.). The ion data repository (e.g., the        size thereof in terms of compounds/ions included therein)        affects the scope of the data curation/verification process to        be performed and determines the available decisions that could        be made when observing data from the component separation and        mass spectrometer system.    -   Historical Training/Empirical Data: Broadly related to the ion        data repository or correction for the state of the component        separation and mass spectrometer system. Historical        training/empirical data mat be used to provide better        characterizations of the state of the component separation and        mass spectrometer system and how compounds/ions respond to this        state, or to characterize the behavior of compounds/ions more        generally on the platform.

The methods, apparatuses and computer program products according toparticular aspects of the present disclosure are premised upon certainoutputs or products, or the conditions of such outputs or products,including:

-   -   Manual Curation/Verification: A general manual        curation/verification process receives data input structured,        for example, as intensity peaks/maxima resulting from the        operation of an arm of the component separation and mass        spectrometer system. The data analysis according to aspects of        the present disclosure is based upon those intensity peaks        included in the library (e.g., within the mass/retention range        of any compound found within the library), but provides another        layer of data where the remaining intensity peaks may be        identified through a relationship with compounds/ions, or        otherwise excluded from the study while providing useful        metadata (e.g., notes about other possible compounds/ions        comprising the actual intensity peaks), analysis (e.g.,        sparsity, artifact), and visualizations (e.g., predictions        relative to actual data).    -   Statistics: In light of the intensity peak/maxima/maximum        predictions, statistics can immediately be computed, which may        take the form of analysis of a “best” version of a compound/ion        (e.g., a minimum relative standard deviation across platforms on        which the compound/ion was observed), normalizations (e.g.,        processing the relative amounts of compounds/ions both presently        and, in principle, against historical norms), comparing results        to historical expectation/prediction, computing z-scores to        identify compounds/ions whose behavior has deviated from        expectation, etc.    -   Biological Inference: Predictions/expectations combined with        statistical analysis drive the biological inference. For        example, identified compounds/ions to which normalizations are        applied and z-scores computed are compared with known pathway        maps to identify up/down regulated biological infrastructure.        From these insights, many analyses, such as disease state, may        be derived.

Therefore, it is to be understood that the disclosure is not to belimited to the specific aspects disclosed and that modifications andother aspects are intended to be included within the scope of theappended claims. Although specific terms are employed herein, they areused in a generic and descriptive sense only and not for purposes oflimitation.

It should be understood that although the terms first, second, etc. maybe used herein to describe various steps or calculations, these steps orcalculations should not be limited by these terms. These terms are onlyused to distinguish one operation or calculation from another. Forexample, a first calculation may be termed a second calculation, and,similarly, a second step may be termed a first step, without departingfrom the scope of this disclosure. As used herein, the term “and/or” andthe “/” symbol includes any and all combinations of one or more of theassociated listed items.

As used herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises”,“comprising”, “includes”, and/or “including”, when used herein, specifythe presence of stated features, integers, steps, operations, elements,and/or components, but do not preclude the presence or addition of oneor more other features, integers, steps, operations, elements,components, and/or groups thereof. Therefore, the terminology usedherein is for the purpose of describing particular embodiments only andis not intended to be limiting.

That which is claimed:
 1. A method of analyzing data for a sample havinga known characteristic, the data for the sample being obtained from acomponent separation and mass spectrometer system, said methodcomprising: analyzing data obtained from the component separation andmass spectrometer system for a reference ion, to determine arelationship between reference ion mass, retention time, and intensity,including intensity as a function of retention time for the referenceion mass, the reference ion having an intensity maxima at acharacteristic retention time for the reference ion mass; adding theanalyzed data for the reference ion to an ion data repository, each ofthe ions in the ion data repository having an intensity maxima within arange of characteristic retention times for a characteristic ion mass;modifying, if the reference ion was previously included in the ion datarepository, the range of characteristic retention times of the referenceion in the ion data repository, according to the characteristicretention time of the intensity maxima for the reference ion; selecting,via a user interface, one or more ions from the ion data repositoryexpected to be included in the sample based on the known characteristicof the sample; comparing, on a display associated with the userinterface, data obtained from the component separation and massspectrometer system for the sample to data for each of the one or moreions selected from the ion data repository to determine whether any ofthe one or more ions is present in the sample; and modifying, via theuser interface, the range of characteristic retention times of each ofthe one or more ions determined to be present in the sample, in the datarepository, according to the characteristic retention time of theintensity maxima for a respective one of the one or more ions determinedto be present in the sample.
 2. The method of claim 1, comprisingincluding the reference ion in the sample.
 3. The method of claim 1,comprising: analyzing data obtained from the component separation andmass spectrometer system for the sample to determine a relationshipbetween sample ion mass, retention time, and intensity, includingintensity as a function of retention time for a selected sample ionmass, the selected sample ion mass being selected via the userinterface; selecting, via the user interface, an ion present in the datafor the sample, the selected ion having an intensity maxima at acharacteristic retention time for the selected sample ion mass;comparing the data for the selected ion to the selected one or more ionsin the ion data repository expected to be included in the sample basedon the known characteristic of the sample, in order to determine anidentity of the selected ion; and modifying the range of characteristicretention times of the ion in the ion data repository corresponding tothe selected ion, according to the characteristic retention time of theintensity maxima for the selected ion.
 4. The method of claim 1, whereinselecting one or more ions from the ion data repository expected to beincluded in the sample based on the known characteristic of the samplecomprises querying the ion data repository via the user interface toselect the one or more ions therefrom based upon a retention time of anintensity maxima of a selected ion from the data for the sample inrelation to the range of characteristic retention times of the intensitymaxima of the one or more ions in the ion data repository.
 5. The methodof claim 1, wherein the sample comprises a plurality of samples in asample run, and wherein selecting one or more ions from the ion datarepository expected to be included in the sample based on the knowncharacteristic of the sample comprises selecting the one or more ionsfrom the ion data repository in relation to ions determined to bepresent in a first one of the plurality of samples, the selected one ormore ions related to ions determined to be present in a first one of theplurality of samples being used for comparison to the data for aremainder of the samples in the sample run.
 6. The method of claim 1,wherein comparing, on a display associated with the user interface, dataobtained from the component separation and mass spectrometer system forthe sample to data for each of the one or more ions selected from theion data repository comprises comparing, on the display, a twodimensional plot of intensity as a function of retention time for thesample to a two dimensional plot of intensity as a function of retentiontime for each of the one or more ions selected from the ion datarepository so as to provide a visual indication of intensity maximatherebetween for determining whether any of the one or more ions ispresent in the sample.
 7. The method of claim 1, wherein modifying, ifthe reference ion was previously included in the ion data repository,the range of characteristic retention times of the reference ion in theion data repository, according to the characteristic retention time ofthe intensity maxima for the reference ion comprises reducing the rangeof characteristic retention times if the characteristic retention timeof the intensity maxima for the reference ion is within the range ofcharacteristic retention times; and determining whether any datadeviation factors in the component separation and mass spectrometersystem require consideration if the characteristic retention time of theintensity maxima for the reference ion is outside the range ofcharacteristic retention times.
 8. The method of claim 1, wherein therelationship between reference ion mass, retention time, and intensity,includes intensity as a function of the reference ion mass for aselected retention time, wherein the adding step comprises adding theanalyzed data for the reference ion to an ion data repository such thateach of the ions in the ion data repository have the intensity maximawithin a range of characteristic ion masses for a characteristicretention time, and wherein the modifying step comprises modifying, ifthe reference ion was previously included in the ion data repository,the range of characteristic ion masses of the reference ion in the iondata repository, according to the characteristic ion mass of theintensity maxima for the reference ion.
 9. The method of claim 1,wherein selecting one or more ions from the ion data repositorycomprises comparing the known characteristic to empirical data includedin the ion data repository, the empirical data including relationalinformation between known characteristics and ions, and determiningtherefrom the one or more ions corresponding to the known characteristicof the sample.
 10. The method of claim 1, wherein, after comparing datafor the sample to data for the one or more ions from the ion datarepository and determining whether any of the one or more ions ispresent in the sample, the method comprises adding empirical dataassociated with the sample to the ion data repository in relation to theany of the one or more ions determined to be present in the sample. 11.The method of claim 1, comprising analyzing data obtained from thecomponent separation and mass spectrometer system for an anchor sample,the anchor sample being defined as a consistent,previously-characterized sample, to determine a component ion of theanchor sample and a relationship between component ion mass, retentiontime, and intensity, including intensity as a function of retention timefor the component ion mass, the component ion having an intensity maximaat a characteristic component ion retention time for the component ionmass.
 12. The method of claim 11, wherein the component ion mass issubstantially equal to the characteristic ion mass of one of the one ormore ions determined to be in the sample, and the method comprisescomparing the intensity maxima for the component ion at thecharacteristic component ion retention time, to the intensity maxima forthe one of the one or more ions determined to be in the sample at thecharacteristic retention time, wherein if the intensity maxima for thecomponent ion and the one of the one or more ions determined to be inthe sample are substantially similar, then the one of the one or moreions determined to be in the sample is designated as an artifact ion inthe sample.
 13. The method of claim 11, wherein the anchor samplecomprises water.
 14. The method of claim 1, wherein the sample comprisesa plurality of samples in a sample run, wherein the method comprisesanalyzing the plurality of samples in the sample run to determine apresence of one of the one or more ions from the ion data repositorydetermined to be present in a first one of the plurality of samples,across the plurality of samples, and wherein if a threshold quantity ofthe samples in the plurality of samples does not include the one of theone or more ions from the ion data repository determined to be presentin the first one of the plurality of samples, then the one of the one ormore ions determined to be present in the first one of the plurality ofsamples is designated as sparse ion in the plurality of samples.
 15. Themethod of claim 1, wherein the sample comprises a plurality of samplesin a sample run, and wherein the method comprises: analyzing dataobtained from the component separation and mass spectrometer system foreach sample to determine a relationship between sample ion mass,retention time, and intensity, including intensity as a function ofretention time for a selected sample ion mass, the selected sample ionmass being selected via the user interface; analyzing the intensity asthe function of retention time for the selected sample ion mass for eachof the samples, across the plurality of samples, to identify anintensity maxima within a predicted range of retention times for eachsample, the predicted range of retention times including an expectedintensity maxima retention time therein for the selected sample ionmass; identifying, for each sample, an actual retention time of theintensity maxima in relation to the expected intensity maxima retentiontime; and determining whether the actual retention times of theintensity maxima of two or more consecutive samples of the plurality ofsamples in the sample run demonstrate an identifiable pattern withrespect to the expected intensity maxima retention time.
 16. The methodof claim 15, wherein the identifiable pattern of the actual retentiontimes of the intensity maxima of the two or more consecutive samples,with respect to the expected intensity maxima retention time, comprisesa shift wherein the actual retention times of the intensity maxima aresubstantially consistently offset from the expected intensity maximaretention time, or a drift wherein the actual retention times of theintensity maxima are offset by a non-constant function from the expectedintensity maxima retention time, and wherein the method comprisescorrecting the offset of the actual retention time of the intensitymaxima of each of the plurality of samples in the sample run accordingto the identifiable pattern.
 17. The method of claim 15, wherein theidentifiable pattern of the actual retention times of the intensitymaxima of the two or more consecutive samples, with respect to theexpected intensity maxima retention time, comprises an offset from theexpected intensity maxima retention time, the offset differing betweentwo subsets of two or more consecutive samples in the sample run, andwherein the method comprises correcting the offset of the actualretention times of the intensity maxima of each of the plurality ofsamples in the sample run according to the identifiable pattern of oneof the two subsets having a majority of the samples in the sample run.18. The method of claim 1, wherein, if comparing data obtained from thecomponent separation and mass spectrometer system for the sample to datafor each of the one or more ions selected from the ion data repositoryto determine whether any of the one or more ions is present in thesample results in none of the one or more ions being present in thesample, then the method comprises resolving an instrument errorassociated with the component separation and mass spectrometer systemand re-running the sample through the component separation and massspectrometer system to obtain replacement data for the sample.
 19. Themethod of claim 16, comprising displaying, on the display associatedwith the user interface, the corrected offset of the actual retentiontime of the intensity maxima of each of the plurality of samples in thesample run according to the identifiable pattern to provide avisualization of the corrected actual retention time of the intensitymaxima of each of the plurality of samples across the plurality ofsamples in the sample run.
 20. An apparatus for analyzing data for asample having a known characteristic, the data for the sample beingobtained from a component separation and mass spectrometer system, theapparatus comprising a processor and a memory storing executableinstructions that, in response to execution by the processor, cause theapparatus to at least perform the steps of: analyzing data obtained fromthe component separation and mass spectrometer system for a referenceion, to determine a relationship between reference ion mass, retentiontime, and intensity, including intensity as a function of retention timefor the reference ion mass, the reference ion having an intensity maximaat a characteristic retention time for the reference ion mass; addingthe analyzed data for the reference ion to an ion data repository, eachof the ions in the ion data repository having an intensity maxima withina range of characteristic retention times for a characteristic ion mass;modifying, if the reference ion was previously included in the ion datarepository, the range of characteristic retention times of the referenceion in the ion data repository, according to the characteristicretention time of the intensity maxima for the reference ion; selecting,via a user interface associated with the apparatus, one or more ionsfrom the ion data repository expected to be included in the sample basedon the known characteristic of the sample; comparing, on a displayassociated with the user interface, data obtained from the componentseparation and mass spectrometer system for the sample to data for eachof the one or more ions selected from the ion data repository todetermine whether any of the one or more ions is present in the sample;and modifying, via the user interface, the range of characteristicretention times of each of the one or more ions determined to be presentin the sample, in the data repository, according to the characteristicretention time of the intensity maxima for a respective one of the oneor more ions determined to be present in the sample.
 21. The apparatusof claim 20, wherein the reference ion is included in the sample. 22.The apparatus of claim 20, wherein the memory stores executableinstructions that, in response to execution by the processor, cause theapparatus to further perform the steps of: analyzing data obtained fromthe component separation and mass spectrometer system for the sample todetermine a relationship between sample ion mass, retention time, andintensity, including intensity as a function of retention time for aselected sample ion mass, the selected sample ion mass being selectedvia the user interface; selecting, via the user interface, an ionpresent in the data for the sample, the selected ion having an intensitymaxima at a characteristic retention time for the selected sample ionmass; comparing the data for the selected ion to the selected one ormore ions in the ion data repository expected to be included in thesample based on the known characteristic of the sample, in order todetermine an identity of the selected ion; and modifying the range ofcharacteristic retention times of the ion in the ion data repositorycorresponding to the selected ion, according to the characteristicretention time of the intensity maxima for the selected ion.
 23. Theapparatus of claim 20, wherein the memory stores executable instructionsthat, in response to execution by the processor, cause the apparatus tofurther perform the step of: querying the ion data repository via theuser interface to select the one or more ions therefrom based upon aretention time of an intensity maxima of a selected ion from the datafor the sample in relation to the range of characteristic retentiontimes of the intensity maxima of the one or more ions in the ion datarepository.
 24. The apparatus of claim 20, wherein the sample comprisesa plurality of samples in a sample run, and wherein the memory storesexecutable instructions that, in response to execution by the processor,cause the apparatus to further perform the step of: selecting the one ormore ions from the ion data repository in relation to ions determined tobe present in a first one of the plurality of samples, the selected oneor more ions related to ions determined to be present in a first one ofthe plurality of samples being used for comparison to the data for aremainder of the samples in the sample run.
 25. The apparatus of claim20, wherein the memory stores executable instructions that, in responseto execution by the processor, cause the apparatus to further performthe step of: comparing, on the display, a two dimensional plot ofintensity as a function of retention time for the sample to a twodimensional plot of intensity as a function of retention time for eachof the one or more ions selected from the ion data repository so as toprovide a visual indication of intensity maxima therebetween fordetermining whether any of the one or more ions is present in thesample.
 26. The apparatus of claim 20, wherein the memory storesexecutable instructions that, in response to execution by the processor,cause the apparatus to further perform the steps of: reducing the rangeof characteristic retention times if the characteristic retention timeof the intensity maxima for the reference ion is within the range ofcharacteristic retention times; and determining whether any datadeviation factors in the component separation and mass spectrometersystem require consideration if the characteristic retention time of theintensity maxima for the reference ion is outside the range ofcharacteristic retention times.
 27. The apparatus of claim 20, whereinthe relationship between reference ion mass, retention time, andintensity, includes intensity as a function of the reference ion massfor a selected retention time, and wherein the memory stores executableinstructions that, in response to execution by the processor, cause theapparatus to further perform the steps of: adding the analyzed data forthe reference ion to an ion data repository such that each of the ionsin the ion data repository have the intensity maxima within a range ofcharacteristic ion masses for a characteristic retention time; andmodifying, if the reference ion was previously included in the ion datarepository, the range of characteristic ion masses of the reference ionin the ion data repository, according to the characteristic ion mass ofthe intensity maxima for the reference ion.
 28. The apparatus of claim20, wherein the memory stores executable instructions that, in responseto execution by the processor, cause the apparatus to further performthe steps of: comparing the known characteristic to empirical dataincluded in the ion data repository, the empirical data includingrelational information between known characteristics and ions; anddetermining therefrom the one or more ions corresponding to the knowncharacteristic of the sample.
 29. The apparatus of claim 20, wherein thememory stores executable instructions that, in response to execution bythe processor, cause the apparatus to further perform the step of:adding empirical data associated with the sample to the ion datarepository in relation to the any of the one or more ions determined tobe present in the sample, after comparing data for the sample to datafor the one or more ions from the ion data repository and determiningwhether any of the one or more ions is present in the sample.
 30. Theapparatus of claim 20, wherein the memory stores executable instructionsthat, in response to execution by the processor, cause the apparatus tofurther perform the step of: analyzing data obtained from the componentseparation and mass spectrometer system for an anchor sample, the anchorsample being defined as a consistent, previously-characterized sample,to determine a component ion of the anchor sample and a relationshipbetween component ion mass, retention time, and intensity, includingintensity as a function of retention time for the component ion mass,the component ion having an intensity maxima at a characteristiccomponent ion retention time for the component ion mass.
 31. Theapparatus of claim 21, wherein the component ion mass is substantiallyequal to the characteristic ion mass of one of the one or more ionsdetermined to be in the sample, and wherein the memory stores executableinstructions that, in response to execution by the processor, cause theapparatus to further perform the step of: comparing the intensity maximafor the component ion at the characteristic component ion retentiontime, to the intensity maxima for the one of the one or more ionsdetermined to be in the sample at the characteristic retention time,wherein if the intensity maxima for the component ion and the one of theone or more ions determined to be in the sample are substantiallysimilar, then the one of the one or more ions determined to be in thesample is designated as an artifact ion in the sample.
 32. The apparatusof claim 21, wherein the anchor sample comprises water.
 33. Theapparatus of claim 20, wherein the sample comprises a plurality ofsamples in a sample run, and wherein the memory stores executableinstructions that, in response to execution by the processor, cause theapparatus to further perform the step of: analyzing the plurality ofsamples in the sample run to determine a presence of one of the one ormore ions from the ion data repository determined to be present in afirst one of the plurality of samples, across the plurality of samples,wherein if a threshold quantity of the samples in the plurality ofsamples does not include the one of the one or more ions from the iondata repository determined to be present in the first one of theplurality of samples, then the one of the one or more ions determined tobe present in the first one of the plurality of samples is designated assparse ion in the plurality of samples.
 34. The apparatus of claim 20,wherein the sample comprises a plurality of samples in a sample run, andwherein the memory stores executable instructions that, in response toexecution by the processor, cause the apparatus to further perform thesteps of: analyzing data obtained from the component separation and massspectrometer system for each sample to determine a relationship betweensample ion mass, retention time, and intensity, including intensity as afunction of retention time for a selected sample ion mass, the selectedsample ion mass being selected via the user interface; analyzing theintensity as the function of retention time for the selected sample ionmass for each of the samples, across the plurality of samples, toidentify an intensity maxima within a predicted range of retention timesfor each sample, the predicted range of retention times including anexpected intensity maxima retention time therein for the selected sampleion mass; identifying, for each sample, an actual retention time of theintensity maxima in relation to the expected intensity maxima retentiontime; and determining whether the actual retention times of theintensity maxima of two or more consecutive samples of the plurality ofsamples in the sample run demonstrate an identifiable pattern withrespect to the expected intensity maxima retention time.
 35. Theapparatus of claim 34, wherein the identifiable pattern of the actualretention times of the intensity maxima of the two or more consecutivesamples, with respect to the expected intensity maxima retention time,comprises a shift wherein the actual retention times of the intensitymaxima are substantially consistently offset from the expected intensitymaxima retention time, or a drift wherein the actual retention times ofthe intensity maxima are offset by a non-constant function from theexpected intensity maxima retention time, and wherein the memory storesexecutable instructions that, in response to execution by the processor,cause the apparatus to further perform the step of: correcting theoffset of the actual retention time of the intensity maxima of each ofthe plurality of samples in the sample run according to the identifiablepattern.
 36. The apparatus of claim 34, wherein the identifiable patternof the actual retention times of the intensity maxima of the two or moreconsecutive samples, with respect to the expected intensity maximaretention time, comprises an offset from the expected intensity maximaretention time, the offset differing between two subsets of two or moreconsecutive samples in the sample run, and wherein the memory storesexecutable instructions that, in response to execution by the processor,cause the apparatus to further perform the step of: correcting theoffset of the actual retention times of the intensity maxima of each ofthe plurality of samples in the sample run according to the identifiablepattern of one of the two subsets having a majority of the samples inthe sample run.
 37. The apparatus of claim 20, wherein, if comparingdata obtained from the component separation and mass spectrometer systemfor the sample to data for each of the one or more ions selected fromthe ion data repository to determine whether any of the one or more ionsis present in the sample results in none of the one or more ions beingpresent in the sample, the memory stores executable instructions that,in response to execution by the processor, then cause the apparatus tofurther perform the step of: resolving an instrument error associatedwith the component separation and mass spectrometer system andre-running the sample through the component separation and massspectrometer system to obtain replacement data for the sample.
 38. Theapparatus of claim 35, wherein the memory stores executable instructionsthat, in response to execution by the processor, cause the apparatus tofurther perform the step of: displaying, on the display associated withthe user interface, the corrected offset of the actual retention time ofthe intensity maxima of each of the plurality of samples in the samplerun according to the identifiable pattern to provide a visualization ofthe corrected actual retention time of the intensity maxima of each ofthe plurality of samples across the plurality of samples in the samplerun.
 39. A computer program product for analyzing data for a samplehaving a known characteristic, the data for the sample being obtainedfrom a component separation and mass spectrometer system, the computerprogram product comprising at least one non-transitory computer readablestorage medium having computer-readable program code stored thereon, thecomputer-readable program code comprising program code for performingthe steps of: analyzing data obtained from the component separation andmass spectrometer system for a reference ion, to determine arelationship between reference ion mass, retention time, and intensity,including intensity as a function of retention time for the referenceion mass, the reference ion having an intensity maxima at acharacteristic retention time for the reference ion mass; adding theanalyzed data for the reference ion to an ion data repository, each ofthe ions in the ion data repository having an intensity maxima within arange of characteristic retention times for a characteristic ion mass;modifying, if the reference ion was previously included in the ion datarepository, the range of characteristic retention times of the referenceion in the ion data repository, according to the characteristicretention time of the intensity maxima for the reference ion; selecting,via a user interface associated with the apparatus, one or more ionsfrom the ion data repository expected to be included in the sample basedon the known characteristic of the sample; comparing, on a displayassociated with the user interface, data obtained from the componentseparation and mass spectrometer system for the sample to data for eachof the one or more ions selected from the ion data repository todetermine whether any of the one or more ions is present in the sample;and modifying, via the user interface, the range of characteristicretention times of each of the one or more ions determined to be presentin the sample, in the data repository, according to the characteristicretention time of the intensity maxima for a respective one of the oneor more ions determined to be present in the sample.
 40. The computerprogram product according to claim 39, wherein the reference ion isincluded in the sample.
 41. The computer program product according toclaim 39, wherein the computer program product comprises program codefor: analyzing data obtained from the component separation and massspectrometer system for the sample to determine a relationship betweensample ion mass, retention time, and intensity, including intensity as afunction of retention time for a selected sample ion mass, the selectedsample ion mass being selected via the user interface; selecting, viathe user interface, an ion present in the data for the sample, theselected ion having an intensity maxima at a characteristic retentiontime for the selected sample ion mass; comparing the data for theselected ion to the selected one or more ions in the ion data repositoryexpected to be included in the sample based on the known characteristicof the sample, in order to determine an identity of the selected ion;and modifying the range of characteristic retention times of the ion inthe ion data repository corresponding to the selected ion, according tothe characteristic retention time of the intensity maxima for theselected ion.
 42. The computer program product according to claim 39,wherein the computer program product comprises program code for:querying the ion data repository via the user interface to select theone or more ions therefrom based upon a retention time of an intensitymaxima of a selected ion from the data for the sample in relation to therange of characteristic retention times of the intensity maxima of theone or more ions in the ion data repository.
 43. The computer programproduct according to claim 39, wherein the sample comprises a pluralityof samples in a sample run, and wherein the computer program productcomprises program code for: selecting the one or more ions from the iondata repository in relation to ions determined to be present in a firstone of the plurality of samples, the selected one or more ions relatedto ions determined to be present in a first one of the plurality ofsamples being used for comparison to the data for a remainder of thesamples in the sample run.
 44. The computer program product according toclaim 39, wherein the computer program product comprises program codefor: comparing a two dimensional plot of intensity as a function ofretention time for the sample to a two dimensional plot of intensity asa function of retention time for each of the one or more ions selectedfrom the ion data repository so as to provide a visual indication ofintensity maxima therebetween for determining whether any of the one ormore ions is present in the sample.
 45. The computer program productaccording to claim 39, wherein the computer program product comprisesprogram code for: comparing, on the display, a two dimensional plot ofintensity as a function of retention time for the sample to a twodimensional plot of intensity as a function of retention time for eachof the one or more ions selected from the ion data repository so as toprovide a visual indication of intensity maxima therebetween fordetermining whether any of the one or more ions is present in thesample.
 46. The computer program product according to claim 39, whereinthe computer program product comprises program code for: modifying, ifthe reference ion was previously included in the ion data repository,the range of characteristic retention times of the reference ion in theion data repository, according to the characteristic retention time ofthe intensity maxima for the reference ion comprises reducing the rangeof characteristic retention times if the characteristic retention timeof the intensity maxima for the reference ion is within the range ofcharacteristic retention times; and determining whether any datadeviation factors in the component separation and mass spectrometersystem require consideration if the characteristic retention time of theintensity maxima for the reference ion is outside the range ofcharacteristic retention times.
 47. The computer program productaccording to claim 39, wherein the relationship between reference ionmass, retention time, and intensity, includes intensity as a function ofthe reference ion mass for a selected retention time, and wherein thecomputer program product comprises program code for: adding the analyzeddata for the reference ion to an ion data repository such that each ofthe ions in the ion data repository have the intensity maxima within arange of characteristic ion masses for a characteristic retention time;and modifying, if the reference ion was previously included in the iondata repository, the range of characteristic ion masses of the referenceion in the ion data repository, according to the characteristic ion massof the intensity maxima for the reference ion.
 48. The computer programproduct according to claim 39, wherein the computer program productcomprises program code for: comparing the known characteristic toempirical data included in the ion data repository, the empirical dataincluding relational information between known characteristics and ions;and determining therefrom the one or more ions corresponding to theknown characteristic of the sample.
 49. The computer program productaccording to claim 39, wherein, after comparing data for the sample todata for the one or more ions from the ion data repository anddetermining whether any of the one or more ions is present in thesample, the computer program product comprises program code for: addingempirical data associated with the sample to the ion data repository inrelation to the any of the one or more ions determined to be present inthe sample.
 50. The computer program product according to claim 39,wherein the computer program product comprises program code for:analyzing data obtained from the component separation and massspectrometer system for an anchor sample, the anchor sample beingdefined as a consistent, previously-characterized sample, to determine acomponent ion of the anchor sample and a relationship between componention mass, retention time, and intensity, including intensity as afunction of retention time for the component ion mass, the component ionhaving an intensity maxima at a characteristic component ion retentiontime for the component ion mass.
 51. The computer program productaccording to claim 50, wherein the component ion mass is substantiallyequal to the characteristic ion mass of one of the one or more ionsdetermined to be in the sample, and wherein the computer program productcomprises program code for: comparing the intensity maxima for thecomponent ion at the characteristic component ion retention time, to theintensity maxima for the one of the one or more ions determined to be inthe sample at the characteristic retention time, wherein if theintensity maxima for the component ion and the one of the one or moreions determined to be in the sample are substantially similar, then theone of the one or more ions determined to be in the sample is designatedas an artifact ion in the sample.
 52. The computer program productaccording to claim 50, wherein the anchor sample comprises water. 53.The computer program product according to claim 39, wherein the samplecomprises a plurality of samples in a sample run, and wherein thecomputer program product comprises program code for: analyzing theplurality of samples in the sample run to determine a presence of one ofthe one or more ions from the ion data repository determined to bepresent in a first one of the plurality of samples, across the pluralityof samples, wherein if a threshold quantity of the samples in theplurality of samples does not include the one of the one or more ionsfrom the ion data repository determined to be present in the first oneof the plurality of samples, then the one of the one or more ionsdetermined to be present in the first one of the plurality of samples isdesignated as sparse ion in the plurality of samples.
 54. The computerprogram product according to claim 39, wherein the sample comprises aplurality of samples in a sample run, and wherein the computer programproduct comprises program code for: analyzing data obtained from thecomponent separation and mass spectrometer system for each sample todetermine a relationship between sample ion mass, retention time, andintensity, including intensity as a function of retention time for aselected sample ion mass, the selected sample ion mass being selectedvia the user interface; analyzing the intensity as the function ofretention time for the selected sample ion mass for each of the samples,across the plurality of samples, to identify an intensity maxima withina predicted range of retention times for each sample, the predictedrange of retention times including an expected intensity maximaretention time therein for the selected sample ion mass; identifying,for each sample, an actual retention time of the intensity maxima inrelation to the expected intensity maxima retention time; anddetermining whether the actual retention times of the intensity maximaof two or more consecutive samples of the plurality of samples in thesample run demonstrate an identifiable pattern with respect to theexpected intensity maxima retention time.
 55. The computer programproduct according to claim 54, wherein the identifiable pattern of theactual retention times of the intensity maxima of the two or moreconsecutive samples, with respect to the expected intensity maximaretention time, comprises a shift wherein the actual retention times ofthe intensity maxima are substantially consistently offset from theexpected intensity maxima retention time, or a drift wherein the actualretention times of the intensity maxima are offset by a non-constantfunction from the expected intensity maxima retention time, and whereinthe computer program product comprises program code for: correcting theoffset of the actual retention time of the intensity maxima of each ofthe plurality of samples in the sample run according to the identifiablepattern.
 56. The computer program product according to claim 54, whereinthe identifiable pattern of the actual retention times of the intensitymaxima of the two or more consecutive samples, with respect to theexpected intensity maxima retention time, comprises an offset from theexpected intensity maxima retention time, the offset differing betweentwo subsets of two or more consecutive samples in the sample run, andwherein the computer program product comprises program code for:correcting the offset of the actual retention times of the intensitymaxima of each of the plurality of samples in the sample run accordingto the identifiable pattern of one of the two subsets having a majorityof the samples in the sample run.
 57. The computer program productaccording to claim 39, wherein, if comparing data obtained from thecomponent separation and mass spectrometer system for the sample to datafor each of the one or more ions selected from the ion data repositoryto determine whether any of the one or more ions is present in thesample results in none of the one or more ions being present in thesample, the computer program product comprises program code for then:resolving an instrument error associated with the component separationand mass spectrometer system and re-running the sample through thecomponent separation and mass spectrometer system to obtain replacementdata for the sample.
 58. The computer program product according to claim55, wherein the computer program product comprises program code for:displaying, on the display associated with the user interface, thecorrected offset of the actual retention time of the intensity maxima ofeach of the plurality of samples in the sample run according to theidentifiable pattern to provide a visualization of the corrected actualretention time of the intensity maxima of each of the plurality ofsamples across the plurality of samples in the sample run.